If successful, it would amount to a major embarrassment for the minority Morrison government on the final parliamentary sitting day of 2018.
A defiant Mr Morrison said such a change would unwind Australia's rigorous offshore processing regime and give the "green light" to a fresh stream of asylum seekers.
"They'll hear the people smuggler who sails up to them and says, 'Guess what, the Australians have changed the legislation, you won't have to stay on Nauru or Manus, all you have to do is get some doctor in Australia to sign it off and it's all good mate, it's all good'," the Prime Minister said.
"And then they'll be on their way. They'll be selling the tickets again. I know this, I lived it, I understand the intelligence that sits behind it."
Mr Morrison claimed the change to medical transfer approvals would "abolish offshore processing as we know it" and "turn it into a transit lounge".
The government gave urgent briefings to members of the crossbench on Thursday morning but Stirling Griff of Centre Alliance confirmed the minor party would not shift its position and would still support faster medical treatment for people on Manus Island and Nauru.
Mr Morrison also claimed the Labor opposition was playing games by "not co-operating" with the government's anti-encryption legislation to give police and spy agencies access to criminals' encrypted messages.
He said Labor had delayed the tabling of a key report last night - a claim Labor emphatically rejected. The opposition has agreed to pass the government's encryption bill despite earlier misgivings, and the bill was being debated in the House of Representatives on Thursday as Mr Morrison was speaking.
Opposition Leader Bill Shorten said: "I’m disappointed by the Prime Minister’s behaviour today but I won’t be distracted. I’ve always taken the view that when it comes to keeping Australians safe, we are all in this together.
"I urge the Prime Minister to stop playing politics and start showing some leadership."
If Mr Morrison loses the vote on refugees, it will be the first time in about 90 years that a government has lost a vote on legislation on the floor of the House. That loss led the then prime minister Stanley Bruce to call an election the next day.
In 2011, when then Labor prime minister Julia Gillard lacked the numbers to pass her so-called Malaysia solution, the then opposition leader Tony Abbott said: "A government that cannot secure its border protection policy from the Parliament is a government which should immediately call an election."