Liberal Democrat MSP Jim Hume said the SNP would have to be "super-careful" in its dealings with the Irish low-cost carrier, which is the Ayrshire gateway's only scheduled airline.
The Government announced plans to bring the airport in to public ownership earlier this week after its owners failed to find a private buyer.
Ministers, including Deputy First Minister Nicola Sturgeon, won cross-party support for the move, which would secure what is both a key UK strategic asset and a crucial hub for high-value jobs.
But South of Scotland MSP Mr Hume, while cautiously backing renationalisation, said: "I have called on the Scottish Government to make sure they fully look at how the big businesses that rely on the airport can play a part in keeping it open and making it profitable.
"Ryanair are a super-profitable company. Even so, they have still been given grants by the Scottish Government.
"Ministers will have to be super-careful they don't get played for fools by the airline and hand over more money.
"If anything, Ryanair should be persuaded to take a bigger role in the rescue of the airport."
The Irish airline - with its high-profile but combative chief executive Michael O'Leary - has a reputation for taking tough negotiating stances with airports.
It has previously had public bust-ups with major airports, and has acted on threats to pull flights after talks on landing fees did not go its way with airports including Stansted in London and publicly-owned Manchester.
Two years ago it axed flights from Girona in Spain after falling out with its owner, the government of Catalunya.
Industry insiders believe that Ryanair, as the only firm flying scheduled flights out of Prestwick, it is in a powerful position to talk tough.
One source said: "Would Alex Salmond really like a public bust-up with O'Leary in a referendum year?"
Mr Hume believes that other businesses based at Prestwick also need to find a way to contribute to the airport's recovery.
Labour leaders in Glasgow, meanwhile, want to make sure nothing is done that would harm Glasgow's main airport at Abbotsinch.
Ryanair declined to comment on Mr Hume's views. But a spokesman said: "We welcome this announcement, which gives certainty to the future development of Prestwick Airport. Ryanair remains committed to Prestwick."
A Scottish Government spokesman said: “Ryanair is clearly a key airport customer and we would intend to conduct detailed discussions with them to establish whether they would consider new services.
“Ministers spoke with Ryanair shortly after the Parliamentary statement to inform them of our intentions."