The driver of a Ford Transit van, a man in his 40s, died at the scene near London Colney, close to St Albans, between junctions 21a and 22.
The crash on the eastbound carriageway happened at 0655 GMT on Friday.
Hertfordshire Police closed the M25 at these junctions for several hours and have appealed for witnesses to contact them.
A woman in her 80s died in a separate crash in Hertfordshire on Friday.
She was riding a mobility scooter which was in collision with a Toyota Hilux truck in Popple Way, Stevenage, at about 1300 GMT.
She was taken to the Lister Hospital, where she later died.
The truck driver, a man in his 20s, was unhurt.
