Former light-welterweight world champion Khan told the MMA Hour television show yesterday he believed mixed martial arts star McGregor could be hurt in what he expects will be a one-sided meeting with Mayweather in Las Vegas.
McGregor has never fought in a professional boxing contest and is a huge underdog against Mayweather, a 49-0 fighter regarded as one of the best boxers in history.
"It's like a tennis player trying to play badminton," Khan said.
"So he (McGregor) should not show too much too balls in this fight. If he starts getting a beating -- step out man," he added.
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Khan's fears reflect wider misgivings by some in the boxing community who believe Saturday's money-spinning superfight should never have been sanctioned on safety grounds.
The head of the Association of Ringside Physicians, Larry Lovelace, is among those who believe Nevada should not have granted a licence to the fight.
"We were very surprised this bout was even sanctioned and was going to be permitted to carry on," Lovelace was quoted as saying by the New York Times.
The Nevada State Athletic Commission, which sanctioned the fight, has a financial interest in the fight going ahead, earning a slice of the gross ticket receipts.
With the bout expected to bring in more than $60 million at the gate, the commission could earn as much as $1.2 million.
But Bob Bennett, the executive director of the commission, hit back at suggestions of a conflict of interest.
"As a regulator, I take offense to the fact that we're approving this fight for fiduciary reasons," Bennett said. "That's totally unfair, and it's simply not true.