"If any time Rand Paul is on the side of an issue, you can automatically assume it's probably a bad one," McCain said. Her comments came after the president decided to pull troops out of Syria in a move backed by Paul.
Several Republicans criticized the decision, which some have argued would leave Kurdish forces vulnerable to attacks from Turkey.
McCain blasted the decision as "abandoning" U.S. allies "to be slaughtered." When co-host Abby Huntsman noted that Paul would appear on the show later in the week, McCain said: "I'm not scared of him."
At one point, McCain said she didn't understand how people like Paul "sleep at night." This was the latest attack McCain fired at Paul, who is considered to have a radically different vision of foreign policy than her father did.
McCain previously boosted an attack that House GOP Conference Chairwoman Liz Cheney, R-Wyo., lobbed at Paul, accusing the Kentucky senator of putting terrorists first.
Trump, on Monday, defended his decision on Twitter. "As I have stated strongly before, and just to reiterate, if Turkey does anything that I, in my great and unmatched wisdom, consider to be off limits, I will totally destroy and obliterate the Economy of Turkey (I’ve done before!)," he said.