The Virgin Group founder has warned that leaving the EU without a deal would result in the closure of British businesses and that the people would suffer as a result.
He said May herself has admitted that her vision of Brexit was not as good as staying in the EU.
"I think Theresa May needs to be 100% honest with the public," Branson told the BBC.
"She's admitted that a hard Brexit would be an absolute disaster for the British people.
"From our Virgin companies' point of view, a hard Brexit would torpedo some of our companies," he said.
Branson pointed out that Virgin Holidays in particular would suffer because the pound taking a hit would result in less people being able to afford to go abroad due to a poor currency exchange.
"If British business suffers, British people will suffer, and it's really really important that people realise that."
Branson was talking from California at the latest Virgin Galactic event, which saw one of his spaceships reach the edge of the earth's atmosphere for the first time.
His comments come at the end of a week in which May backed out of a parliamentary vote on her Brexit deal and also faced a vote of no confidence from her party, which she survived.
May is currently seeking assurances from EU leaders regarding the contentious backstop issue with the Irish border and a vote on her deal will now likely take place in January.