The health secretary told MPs he was made aware on 31 January 2020 that up to 820,000 people could die from COVID-19 based on a comparison with the Spanish flu pandemic, but that overruling a scientific consensus would have been a "huge decision" to take.
Giving evidence to the Health and Social Care Committee and Science and Technology Committee, Mr Hancock said experts believed people would put up with lockdown measures for "only a limited period", but that this "proved actually to be wrong".
"I asked for a reasonable worst-case scenario planning assumption, and I was given the planning assumption based on Spanish flu.
"And it was signed off at COBRA on January 31, and that was a planning assumption for 820,000 deaths, and I was determined that that would not happen on my watch," he said.
The first nationwide lockdown in the UK was imposed on 23 March, more than seven weeks after Mr Hancock said he received this modelling.
But, despite telling the committee that by 9 March "the data started to follow" this modelling, the health secretary said an earlier lockdown would have meant going against scientific advice.
"Critically, the clear advice at the time was that there's only a limited period that people would put up with it, would put up with lockdown. Now that proved actually to be wrong," he said.
The health secretary added: "These are huge decisions; to take those decisions against the scientific advice is an even bigger decision to take."
But Prof Stephen Reicher FBA, professor of social psychology at the University of St Andrews, said the health secretary's claim was "simply untrue".
"Matt Hancock claims that earlier lockdown would have gone against the scientific consensus and that 'the clear advice at the time was that there was a limited time was that there was a limited period that people would put up with it'. This is quite simply untrue," Prof Stephen said.
"It is an old claim that has been comprehensively debunked. Such advice didn't come from the government's own behavioural advisory group. Such an idea was publicly disputed by behavioural scientists.
"So I don't know what Hancock means when he talks about 'the clear advice at the time' but it was not the scientific advice, and certainly not the behavioural science advice."
The health secretary was questioned by MPs two weeks after Dominic Cummings, the PM's former chief aide, claimed he "should have been fired for at least 15 to 20 things including lying".
Mr Hancock denied claims he lied to the prime minister over the COVID care homes crisis and said "you can't respond to a pandemic by pointing fingers".
Asked if he knowingly lied to the prime minister about anything during the pandemic, Mr Hancock said: "No."
One of the most explosive claims Mr Cummings made when giving his committee evidence was that the health secretary told Mr Johnson in March that people in hospital would be tested before returning back to care homes.
Addressing this allegation, Mr Hancock told MPs: "We set out a policy that people would be tested when tests were available - and then I set about building the testing capacity to be able to deliver on that."
The health secretary added that the government followed the "clinical advice" at all times, which included three key points:
• The NHS at the time didn't have the testing capacity
• Tests on asymptomatic people could return a false negative
• As tests were taking four days to turn around, patients could go back into care homes and then later test positive
He added that the "strongest route" of the virus into care homes was through community transmission, noting estimates suggest 1.6% of the transmission into care homes came from hospital discharges.
"The challenge was not just that we didn't have the testing capacity, but also that the clinical advice was that a test on somebody who didn't have any symptoms could easily return a false negative and therefore give false assurance that that person didn't have the disease," Mr Hancock said.
"Right from the start we knew that people living in care homes were amongst the most vulnerable and we did all that we could to support them."
But UNISON general secretary Christina McAnea said "there was no protective ring" around the social care sector which was "left completely high and dry".
"This is not a government that did its utmost to protect the care sector. Big mistakes were made with deadly consequences. That's why the public inquiry must start gathering its evidence sooner than next year," she said.
Mr Hancock also added that it was "telling" that Mr Cummings had not yet submitted any evidence to the committee to support his allegations.
Earlier in the evidence session, Conservative chairman of the Science and Technology Committee Greg Clark said members had not received any written evidence from Mr Cummings to back up his claims or any explanation as to why it had not been provided.
Striking back at Mr Cummings, Mr Hancock said the government "has operated better in the past six months" since the PM's former senior aide left his position in Downing Street.
Another claim rejected by the health secretary is that there was a national personal protective equipment (PPE) shortage during the pandemic.
He told the committee that while there were, at times, "local pressures" with getting PPE, there was "never a national shortage" - despite the "huge demand".
But Dr Rosena Allin-Khan called the health secretary's remark "insulting".
On a post on social media, the Labour shadow health minister said: "Matt Hancock says there was never a shortage of PPE. It's insulting to all the frontline staff who didn't have the right masks or who were given inferior gowns. They were put at unnecessary risk."
Mr Hancock also disputed that there was ever a shortage of testing. He told MPs: "Testing was at no point scaled down, on the contrary, we were driving up testing capacity all the way through."
And the health secretary also made clear in his evidence that he takes "full responsibility" for the decisions taken over the last 15 months, but that he was "guided by the science".
"I take full responsibility for the decisions not only that I take, but that are taken in my name as secretary of state, across the health family and the NHS, Public Health England, in the department.
"And I know the prime minister feels very strongly the same. But of course you are guided by the science," he said.
Telling MPs he had tried to act with "honesty and integrity" throughout dealing with the pandemic, Mr Hancock added: "Throughout this I have got out of bed every morning with the view and the attitude that my job is to do everything I could to save lives and get this country out of the pandemic."
In his evidence session in May, Mr Cummings labelled Mr Hancock's target to reach 100,000 tests a day by the end of April 2020 "incredibly stupid", saying it took away the government's focus.
But hitting back at this accusation, the health secretary told the committee the prime minister had always been behind the target.
"The purpose of the target was to galvanise the system - it worked," he said.
"The prime minister was absolutely four-square behind me and gave me his full, whole-hearted support in hitting this target because he, like me, knew we needed a radical increase in testing."
Meanwhile, on a visit to Batley and Spen - where a by-election is due to be held in a few weeks - Labour leader Sir Keir Starmer urged the health secretary to answer the "very serious allegations" made against him by Mr Cummings.
"What I want to see today is Matt Hancock answer those allegations.
"That's what he should do. There are many allegations. The most important are the ones in relation to care homes and this pretence that they put a sort of protective ring around care homes which didn't happen," he said.