Mr Perrottet was one of the 11 MPs who rose on Friday to indicate they would vote against a bill that would give terminally ill people access to voluntary assisted dying.

Twenty other politicians spoke in favour of the bill, which if passed would bring NSW into line with every other state.

The premier said the issue was not "abstract" to him as his grandmother, aged in her nineties, is dying of pancreatic cancer.

"I sat next to her, holding her hand. I could tell that she was in great pain and that she wanted it to be over.

"I got a sense, as much as anyone can have, why those in such pain would want to end it quickly."

But Mr Perrottet said the proposed laws mark a "threshold moment" and the state should instead improve the quality of palliative care.

While the bill currently restricts euthanasia to terminally ill people who would die in no more than 12 months, the premier said it opens the door for euthanasia in other circumstances.

"This debate is fundamentally about how we treat that precious thing called human life," he said.

"If we crossed this threshold, this parliament should be under no illusions as to what it would do."

All MPs have been afforded a conscience vote.

Member for Wagga Wagga Joe McGirr said the bill went against "the sanctity of human life", while Nationals MP Stephen Bromhead said it was "open to abuse".

Opposition leader Chris Minns said he was "in the minority" within the NSW Labor party but he would also vote against the bill.

"I am not convinced any legislation can prevent an individual choosing to die in response to pressure, coercion or duress caused by others," Mr Minns said.

"No legislation, even one crafted with the best of intentions such as this bill, can prescribe against the conduct of people with bad intentions."

His Labor colleague Jo Haylen, one of the record 28 co-sponsors of the bill from across the political spectrum, said the legislation is packed with strict safeguards.

Two doctors will have to assess applicants, and the bill makes attempting to induce a person to apply for voluntary assisted dying a criminal offence.

"It is a considered bill," Ms Haylen said.

Palliative care is important but it cannot manage the pain of many terminally ill people, she said, citing stories from her constituents, including one with an aunt who was forced to take her life in secrecy in the absence of euthanasia laws.

Many MPs voting in favour of the bill read out letters from members of their electorate who had watched family members die in pain and without dignity.

Labor MP David Harris made a speech about his father who endured a "terrible time" when he was dying of cancer.

"Unfortunately because of current laws he had to resort to telling the doctors to end any further treatment and to up his painkillers so that he would go peacefully in his sleep," Mr Harris told the parliament.

"That is not what he wanted because he thought that was putting a responsibility on to them, that wasn't the right thing."

Multiple MPs cited polling from their electorates showing overwhelming support for the legislation, including Liberal MP Andrew Constance who described the bill as "compassionate".

"As someone who is religious, albeit quietly, this goes to the very heart of what my beliefs and faith are all about," Mr Constance said.

Nationals MP Christopher Gulaptis said the debate was not about "sanctioned murder" as there was strict eligibility criteria.

"It is not for everyone and you can't bump off Uncle Charlie to get your hands on the inheritance," Mr Gulaptis said.

Debate will continue into next year, after the government and Labor agreed to refer it to an upper house inquiry.

Australian Associated Press