TWO members of the one family were killed and another two hospitalised after an early morning crash on the Pacific Highway north of Port Macquarie

Another man was lucky to survive the crash in the Cooperabung Ranges and was airlifted to a Newcastle hospital having been trapped in his truck for nearly an hour after the 5am crash.

The 40-year-old mother and her 12-year-old-daughter in the southbound Hyundai sedan were killed. The woman's 47-year-old husband and 14-year-old daughter survived.

At the northern edge of the ranges, near Barrys Creek Road, emergency services moved urgently throughout the morning.

Fragments of the Hyundai were scattered across the southbound lane, while 150 metres north the truck lay crushed on its roof, with the crumpled metallic shell resting against the safety barrier.

Police said the vehicles were travelling in opposite directions when they crashed into each other.

The truck driver had severe head injuries and was taken to Port Macquarie Base Hospital, before being airlifted to John Hunter Hospital at 8am.

A NSW Health spokeswoman said he was transferred in a critical condition, while the Hyundai's surviving passengers were treated in the emergency department and then discharged.

Crash investigations units from Kempsey and Newcastle moved with purpose through the wreckage, as they tried to make sense of the horror.

Inspector Mick Aldridge described the crash's details, and said none of those involved were locals.

He also said the single carriageway location was a problem area on the Mid-North Coast.

"We had a recent fatality just five kilometres down the road from here," he said. "It's an area that people don't know, it is of concern like many parts of the highway."

Kempsey police were first on the scene at 5.25am, and were followed by State Emergency Services units from Kempsey and Port Macquarie shortly after.

SES unit controller Kevin Sherwood said it was an arduous operation which took many hours.

He praised volunteers for their speed and professionalism, but lamented the terrible loss.

One lane of alternating traffic was opened at 10.30am, and regular flow was expected later in the afternoon.