Annabelle Falkholt, 21, and her actress sister Jessica Falkholt, 28, were seriously injured in the crash, which claimed the lives of their parents and a 51-year-old man driving the other car.

The women remained in critical conditions in separate Sydney hospitals on Wednesday.

A fire "incinerated" both cars involved in the crash after the sisters were pulled to safety. Their parents, whose ages were not released, could not be saved.

Chief Inspector Phil Brooks, of the NSW Police traffic and highway patrol command, said crash investigators went to a home in Ryde before they located relatives of the family at several other Sydney addresses.

"And sadly, those family members are travelling to Liverpool and St George hospitals to engage with their loved ones who are very much in a critical condition at the moment," Chief Inspector Brooks said.

Jessica Falkholt has starred in Home and Away, with a recurring part in 2016, and will appear in the upcoming Australian film Harmony.

She is a graduate of UNSW and the National Institute of Dramatic Art, and has worked in production for Channel Seven, according to an online profile.

The fiery Princes Highway crash on Tuesday has headlined a deadly festive season on NSW roads, with 21 people killed since the start of Operation Safe Arrival on December 16.

It includes another three on Boxing Day after a 25-year-old woman was killed when her car hit a tree near Taree, a 43-year-old man who died when his Ford Falcon ran into a parked semi-trailer at Emu Plains and a 23-year-old Dubbo woman who suffered horrific head injuries when she fell from a moving four-wheel drive at Peak Hill.

The deaths, almost triple the number for the same period last Christmas, have senior police flabbergasted.

"This Christmas-New Year period is meant to be a time of happiness, to spend time with family. And sadly, for many, this has resulted in tragedy," Chief Inspector Brooks said.

"So far, during the operation, 21 lives have been lost. Those families directly impacted by road trauma on NSW roads."

He later added: "Everyone who has been on our roads leaves home in the hope they can get back there [or] to their destination.

"Sadly, for 21 people so far during Operation Safe Arrival that hasn't occurred courtesy of what is a very clear lack of personal responsibility on our roads.

"Out of the 21 lives lost so far, 11 of those deaths have been from people leaving the road in a vehicle crashing either into a tree or a telegraph pole sadly losing their lives on the side of the road.

"Three other deaths are courtesy of people drifting across to the other side of the road resulting in head-on crashes [and] sadly more lives lost on our roads in sad and tragic events."

The spike in deaths is not the only worry for police, with highway patrol police handing over more than 13,500 speeding fines and charging 433 motorists with drink-driving.

"Luckily for those drivers, they get to go home to their families," Chief Inspector Brooks said.

"Sadly, for the 21 lives lost so far during the operation those families will no doubt be feeling the pain and suffering of losing a loved one this close to Christmas."

with Georgina Mitchell