Westgate Highway Patrol officers are appealing for witnesses to a collision in Williams Landing on Thursday 19 November.
Investigators have been told a white semi-trailer truck was driving inbound on the Princes Freeway after passing the Forsyth Road overpass about 12.40pm.
It is believed the truck drove through the centre median strip and struck a white Honda CRV as it travelled across all outbound lanes of the freeway before coming to a stop in a car park in Wallace Avenue.
The driver and sole occupant of the Honda, a 33-year-old Narre Warren man was taken to hospital with serious injuries.
The truck driver, a 58-year-old man was conveyed to hospital with minor injuries.
Investigators are urging anyone who was driving inbound along the Princes Freeway who may have witnessed the truck travelling prior to the collision or with dash cam footage to contact Crime Stoppers on 1800 333 000 or submit a confidential report online at www.crimestoppersvic.com.au.