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.