Campaigners say the former Volkswagen car showroom in Iffley Road is being used as "Oxford's unofficial homeless shelter".
The site is currently home to 14 people and has been vacant for two years.
But Wadham College hopes to redevelop the building into student accommodation.
Campaigners have asked for the site to be officially designated as homeless housing.
"I don't want to see anyone freezing to death in the city that's my home," said one supporter, Miranda Shaw.
"That is something that has happened in other cities around the country and I think that is totally unacceptable."
Lewis Cairns, who is homeless and living in the squat, said: "It's a bit of a godsend really, I feel like I can get somewhere now.
"I can start applying for university and get things done."
A spokesperson for Wadham College said it was "exploring everything" and had not decided whether to take legal action.
It added its primary focus was "the safety implications for the homeless who have moved in" and said it had a longstanding relationshop with the Gatehouse homeless project.
A statement said: "The college will be making every effort to speak to representatives of this homeless group as well as local residents, safety experts and the site developers.
"As part of [redeveloping the site], Wadham College has undertaken to contribute more than Â£900,000 towards social housing provision in Oxford.
"The college regularly fundraises for homeless organisations and we donated much of the furniture from the Iffley Road site to a homeless charity."
A college that owns a building used by squatters as a homeless shelter has said it is "investigating all options", including legal action.