A 28-year-old Blackstone Heights woman was killed after crashing into an oncoming vehicle on the Bass Highway on Monday night.

The woman was heading to Launceston when her orange Ford Festiva collided with a white ute travelling in the opposition direction.

She died at the scene.

Both cars were "significantly damaged" during the collision, but the passengers of the second vehicle escaped with non-life-threatening injuries.

The 42-year-old man and 35-year-old woman from Gunns Plains were taken to hospital, but were reported as being in a stable condition.

Tasmania Police Inspector Ruth Orr said it was still unclear how the female driver ended up in the other lane, but speed was not believed to have been a factor, and the weather was "fine and clear".

"There's a number of factors that could contribute to this crash, which are being investigated, and that includes alcohol and drugs, driver fatigue, and possibly inattention," she said.

"All occupants involved were wearing seatbelts."

The highway was closed for several hours as a result of the crash on Monday night, with investigators back at the scene on Tuesday afternoon.

Those investigators are expected to return to the site again on Wednesday morning, which will likely see the highway closed for about half an hour from 10.30am.

As part of the investigation, police are seeking witnesses who may have seen either vehicle before or at the time of the crash, or anyone who may have dash cam footage.

The crash took place about 7.40pm.

"We are looking at getting some surveillance footage from the service station nearby, and we are asking if anyone did see either of those vehicles to please contact police," Inspector Orr said.

At least eight people have now been killed on the notorious stretch of the Bass Highway in the past decade, prompting renewed safety calls.

Since late 2009, multiple serious crashes have been reported along the highway roughly between Elizabeth Town and Parramatta Creek, with at least five ending in tragedy.

Prior to Monday night's crash, a 59-year-old Victorian motorcyclist was killed in October 2016.

A year earlier, an elderly North-West woman died after attempting to pull out of Christmas Hills Raspberry Farm.

The 80-year-old collided with another vehicle on the highway, and was killed instantly.

In 2009, teen boxing champion Jesse Crack crashed head-on into another vehicle on the highway. The 17-year-old was hospitalised after the collision, but later died.

The crash also claimed the life of 54-year-old Devonport man Glenn Pipkin.

Meander Valley mayor Wayne Johnston said the state government needed to "prioritise" safety upgrades for the highway.

"It is a section of road that needs upgrading, I have had truck drivers carting heavy loads complain to me in the past about the condition of the road, and I know some roadworks have been done, but it would be good for the state government to bring it forward as a priority," he said.

"It is extremely disappointing and distressing for the families of those who have perished on that stretch of road, and for the emergency workers who have to attend these crashes."

While at least three of the fatal crashes in the past decade involved a driver on the wrong side of the road, Infrastructure and Transport Minister Michael Ferguson said the section of highway near Elizabeth Town had been identified as a priority.

"I am advised the Bass Highway meets national standards and guidelines for the category, function and speed of the road," he said.

"The work for prioritising and planning the proposed improvements will commence next year and will be used to inform any future funding considerations.

"My heart goes out to the loved ones of this young woman who tragically died."

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