Officers were called to the scene at about 3.20am on Friday, Thames Valley Police said.
The collision happened on the northbound carriageway between the junctions for Peartree and Islip.
"Officers attended the scene where sadly the pedestrian, a man aged 35, had died," the force said in a statement.
"Next of kin have been made aware and are being supported by specialist officers."
One lane of the A34 remains closed while road surface repairs are completed.