Two semi-trailers and three cars have been involved in a smash on the M4 near the Silverwater exit between Auburn and Silverwater.
Witnesses said they heard up to 10 loud bangs when the semi-trailers, driving away from Sydney, collided with the cement barrier on the motorway near the Silverwater exit at 12.20pm.
A white falcon ute, also driving away from Sydney, flipped over and caught fire.
Advertisement Witnesses said they saw 10-15 men trying to rescue the driver, who was screaming.
Emergency services have taken the man away in an ambulance.
One of the semi-trailers, with "Versa Cola" written on it, smashed through the central barrier and collided with a white Hyundai station wagon that was on the city-bound side of the road.
A fifth car, a black four-wheel-drive, was involved in the accident but drove off.
Police blocked off the M4 both westbound and eastbound and traffic was built up about 10 kilometres each way.
About 2pm two westbound lanes were reopened, leaving one closed, while all citybound lanes remained blocked.
A spokeswoman for the Ambulance Service of NSW said two people were taken to Westmead Hospital. One had minor injuries and another had cuts on the head. Both were in stable conditions.
Candy Goonan, who lives nearby, said she heard five bangs, then a screech, then another five bangs.
"It was so loud it scared my cats from the driveway," she said.
Ms Goonan said only yesterday there was a three-car pile up in the same area.
"It's a dangerous street," she said.
Another resident, Joseph Taouk, said he heard also heard 10 bangs and the truck flip.
He said the man trapped inside the flipped ute was screaming for help.
A NSW Police spokesman said that there were initial reports of one man suffering head injuries and another person trapped in a car.
The Transport Management Centre advised motorists to avoid the area and use Parramatta Road as an alternative.
Westbound motorists are being diverted off the M4 via Silverwater Road, while eastbound motorists are being diverted via Church Street.
The speed limit through the reopened lanes is 40km/h so motorists are advised to allow extra travel time and use caution in the area.