A Suzuki Swift was going northbound at Aldershot, near Maryborough about 5.40pm when it collided with a truck going the other way.
The truck caught fire during the crash, with emergency services quickly descending on the scene.
The four people inside the Suzuki were all taken to hospital, including a 28-year-old man who received life-threatening head injuries.
A young girl also received life threatening injuries to her head, limb and chest, and was taken to Hervey Bay Hospital.
The driver, a 25-year-old woman, was also transported in a stable condition.
An infant boy recieved head injuries but was stable according to a Queensland Ambulance spokesperson.
The driver of the truck, a man in his 40s, sustained minor injuries.
The highway was closed in both directions, but has since been reopened.
Forensic crash investigators are attempting to find the cause of the crash.