The truck driver involved in a multi-vehicle crash that has left 10-year-old boy dead and at least five others injured is being interviewed by police.

The boy died at the scene of the accident, which occurred on the M5 just east of Belmore Rd in Riverwood about 8.20am.

The crash forced citybound traffic to a standstill from peak hour until mid afternoon, although all eastbound lanes have now reopened.

NSW Ambulance Acting Superintendent Gavin Wood said veteran paramedics were shocked by the scene of the accident involving three cars and a truck.

"On arrival, we were confronted by quite a terrifying scene involving four persons," Acting Superintendent Wood said.

Early investigations indicated the truck had collided with the rear of a Subaru and partially travelled over it, before hitting a third and fourth vehicle.

The 10-year-old boy who was in the rear of the Subaru was killed, while a 12-year-old female passenger in the front seat was injured and taken to Sydney Children's Hospital.

The female driver was taken to hospital but has since been released.

Superintendent Paul Glinn, acting assistant commissioner for the Highway Patrol, said investigators were now looking at causal factors.

"Police have taken possession of a mobile phone that was in the heavy vehicle and that will be subject to forensic analysis in the coming days," Supt Glinn said.

The truck, which consisted a prime mover and trailer, has also been seized and will be subject to mechanical examinations.

The drivers of all four vehicles - two men and two women - were taken to hospital for mandatory testing and treatment of non-life threatening injuries.

The incident is being investigated by the Metropolitan Crash Investigation Unit and police are appealing for witnesses and anyone with dash cam video to come forward

Contact Campsie Police Station on (02) 9784 9399 or Crime Stoppers on 1800 333 000.