"Pastor (Terry) Jones' threats to burn the Koran will put American service men/women in danger - for their sake, please don't do it!" McCain said on his Twitter feed, which has about 1.7 million followers.
The Arizona senator's comments came a day after his 2008 White House running mate, Sarah Palin, said on her Facebook page that the Koran burning should not go forward amid a chorus of global outrage.
McCain became the latest high-profile Republican to warn against plans to torch Islam's holy book at an event to mark nine years since the September 11, 2001 terrorist attacks by the extreme Islamist al-Qaeda network.
On Wednesday, House Republican Minority Leader John Boehner told ABC television that "just because you have a right to do something in America does not mean it is the right thing to do".
"We're a nation of religious freedom. We're also a nation of tolerance. And I think in the name of tolerance, people ought to really think about the kind of actions they're taking," said Boehner.
"I just think that it's not wise to do this in the face of what our country really represents," said Boehner.
Some top Republicans have kept quiet, including former president George W. Bush, who worked hard during his eight years in office to tamp down hostility towards Muslims in the United States.
Boehner and Palin each likened Jones's plans to a project to build a community centre to include a mosque some two blocks from the site of the September 11 attacks in New York City, saying both were inappropriate.