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Police were called to the M65 between junction 10 and 9 westbound, near Burnley, just after 1.20am today (May 22).
The man had been hit by a Dacia Sandero car and suffered serious leg and head injuries.
He was taken to Royal Preston Hospital for treatment.
The motorway re-opened at about 5.50am.
Police are now appealing for witnesses to come forward to assist with their investigation into the crash.
A spokesperson for Lancashire Police said: “We were called at 1.23am today to the M65 westbound between junctions nine and 10, to reports of a road traffic collision.
“A car was in collision with a pedestrian.
“The pedestrian suffered serious head and leg injuries and was taken to the Royal Preston Hospital.
“The carriageway was reopened at approximately 5.50am.”
Sgt David Hurst added: “This was a serious incident which resulted in a pedestrian receiving significant injuries.
“We are investigating why the pedestrian was on the carriageway and are appealing for any witnesses to the collision and who were in the surrounding area to come forward.”
Anyone who witnessed the collision or who has dashcam footage from the motorway around the time is asked to contact police by calling 101 – quoting log 57 of May 22 – or email 2856@lancashire.police.uk.
Information can also be passed anonymously to independent charity Crimestoppers by calling 0800 555111.
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