Orban has long accused Hungarian-born Soros of meddling in central and eastern Europe and of seeking to undermine the continent by backing mass immigration.
"Cheating is cheating... It doesn't matter if you are a billionaire, you are not above the law," Orban said during an interview on public radio.
The Central European University (CEU), set up in 1991 after the end of communism and part-funded by Soros, said in a statement that it "utterly rejects" Orban's allegations.
His anti-Soros quest intensified on Tuesday with the publication of proposed legislation that would tighten rules for foreign-based universities operating in Hungary.
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The CEU believes it is the main target of Orban's plan and has said that its existence is under threat.
Orban said Friday that the aim was to stop universities from countries outside of the European Union from being able to cheat students.
He said it followed checks on 28 foreign institutions that uncovered irregularities. "Several foreign universities are breaking the rules, including the Soros university," he said.
The proposed new rules would ban the awarding of Hungarian diplomas without an international agreement between national governments.
Institutions must also have operations in their home country.
The future of the CEU, which does not have a US campus, now "depends on talks between the governments of Hungary and the United States," Orban said.
"We have been lawful partners in Hungarian higher education for 25 years and any statement to the contrary is false," it said.
In an interview with AFP yesterday, the CEU's president and rector Michael Ignatieff called the proposed new rules "unacceptable, targeted at CEU, and an attack on academic freedom".
"We will be open for business and accept students and teach them next year, if I have to teach in a tent in a park in Budapest I will do so," said the former Canadian politician, insisting that the university "will not be bullied".
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