DeMint dismissed attacks that portray Romney as a greedy capitalist, calling them "political talk" but he told ABC News Romney needs to better explain layoffs that occurred while he ran Bain Capital and express empathy for those workers.
"I know I had to do it a few times in my career and I had sleepless nights and it killed me to do it but I was doing it to save the other employees in my company and keep it going," DeMint said. "If he doesn't explain this well he's going to see this again if he's the nominee in the general election."
Romney has repeatedly said companies Bain invested in went on to create 100,000 jobs but his campaign has declined to say how many employees were laid off during that time.
Any political attack ad that targets Mitt Romney's tenure at Bain "really bothers" DeMint.
"Successful companies have leaders who are willing to make hard, difficult, unpopular decisions for the good of the company," DeMint told ABC News Radio in an interview to promote his new book "Now or Never: Saving America from Economic Collapse."
Sen. DeMint said he would not endorse a GOP candidate before Saturday's primary in South Carolina, though he said he would not completely rule it out.
"The only way I could have been dragged into it is if we had two candidates and one was just completely on the wrong track and the other was moving in the conservative direction."
DeMint said he has not talked to Romney in a while but emails frequently with him and with Ron Paul.
"I think he is in it to win or at least in it for the long haul."