Labor, the Greens and crossbench senators want to look at alternatives to deregulating university fees.
Key crossbench senators will help Labor explore how universities can be helped without deregulating fees.
The move comes as another university vice-chancellor broke ranks to express doubts over the merits of deregulation.
Labor's Kim Carr and crossbenchers Nick Xenophon, Jacqui Lambie and Ricky Muir intend to ask the Senate on Wednesday to set up another inquiry into higher education.
They want to look at what alternatives there are to deregulation in order to maintain a sustainable higher education system.
The support from senators Xenophon and Muir is significant because the government is wooing them as it makes a second attempt to pass its higher education reforms, including deregulating fees.
Senator Muir sided with the government to continue debate on the changes in December, when they were defeated.
It is understood the inquiry will have the support of the Greens and the Palmer United Party.
If the committee goes ahead, it will report back on March 17.
The second version of the deregulation package was debated in the House of Representatives for much of Tuesday, with 49 MPs lining up to have their say.
The presidents of the National Union of Students and the Council of Australian Postgraduate Associations are lobbying MPs and senators to oppose the bill.
"If this doesn't pass, it doesn't mean that higher education is going to fall apart," NUS national president Rose Steele told AAP.
CAPA president Harry Rolf described the government's plan as a "blunt instrument to fix a nuanced problem".
Meanwhile, Victoria University vice-chancellor Peter Dawkins has revealed he is lukewarm about the government's plans.
He says "unfettered deregulation" with no safeguards would seriously risk disadvantaging many students.
Professor Dawkins would rather see "managed deregulation", such as caps on fees or tapered subsidies.
Nationals senator Bridget McKenzie, who chaired the committee's previous inquiry into the higher education package, told AAP she's always eager to hear new evidence or about new impacts.
But she said it was also important to remember the entire higher education sector had been comprehensively reviewed in a series of inquiries going back to the Bradley Review in 2008.
Senator McKenzie hopes the fate of the deregulation package can be decided by the end of March to give more certainty to students, parents and universities.