The eastbound carriageway of the A63 Clive Sullivan Way is closed from the A1034 to A15 and is likely to remain so until midday.
It comes after the pedestrian was badly hurt in the collision with a lorry between Melton and Brough.
Diversions are in place.
Humberside Police said: "We were called by the ambulance service at 5.30am today who reported that a pedestrian had been in collision with a lorry on the eastbound carriageway between Melton and Brough.
"The man, who has not yet been identified, has been taken to Hull Royal Infirmary for treatment and our teams are investigating the circumstances of the incident.
"Our thoughts are with his family and loved ones."