A multi-viehcle crash closed the Hume Highway near Violent Town in regional Victoria. Image: Nine News

A truck driver has been killed in a serious multi-vehicle crash that shut a section of a major Australian highway for several hours.

Emergency services rushed to the Hume Freeway near Harrys Creek Road at Violet Town, about 180km north of Melbourne, at 1.25pm on Friday following a collision.

Police believe a B-double truck collided with a road workers truck then veered across a median strip where it clipped a car before it roll and caught fire.

“The driver of the B-double truck, who is yet to be formally identified, died at the scene,” a police spokesman said.

A truck crash has closed the Hume Highway at Violent Town. Picture: 9News

The Hume Freeway was closed in both directions while emergency services responded to the incident.

An Ambulance Victoria spokesman said two adults and two children were transported by road to a Wangaratta hospital in a stable condition following the crash.

A spokesman said paramedics rushed another man in his 50s to Goulburn Valley Health with minor injuries.

9News has captured the extent of the crash, showing the truck resting on its side and emergency vehicles swarming the scene.

According to VicTraffic, motorists were advised to take lengthy detours while emergency services responded to the incident.

Several people have been rushed to hospital in a stable condition following the serious crash involving multiple vehicles. Picture: 9News

Northbound motorists had to detour via the Goulburn Valley Highway through Seymour to Shepparton then return via Benalla on the Midland Highway.

Southbound traffic was instructed to exit the Hume Highway at Violet Town and use Murchison-Violet Town Road to the Goulburn Valley Highway, before rejoining the Hume in Seymour.

Police are still investigating to determine the exact circumstances surrounding the collision.