Billionaire investor and Hillary Clinton-supporter Mark Cuban said Republican presidential nominee Donald Trump doesn't know how Obamacare works.

In an interview on CNBC's "Squawk Alley" on Tuesday, Cuban compared President Obama's universal health care plan to "one of the biggest start-ups of all time," saying it'll go through "fits and difficulties." He added that Trump has not grasped the basics of the Affordable Care Act, making it impossible to have an "open and candid discussion with him about health care."

"He's demonstrated again and again he doesn't even understand what Obamacare really is or how it works," he said.

He admits the increases in premiums are a concern for people in some states, but said it is mainly because of insurance companies that entered the market and underpriced the first several years, missing certain projections.

"That's not unusual for a start-up," he said. "It doesn't help the people in those states, obviously, it's very painful for them ... but (Trump has) made no effort to learn those things."

Cuban added that Clinton's understanding of "how government works" will at least give him — and anyone else who disagrees with Clinton — the opportunity to lobby against her on issues like free college tuition, compared with Trump.

"I don't have that same confidence that Trump understands his position, understands how government works, understands the concept of checks and balances," he said. "I don't have the confidence that I could just lobby against him blurting things out."