The Prime Minister told a business audience in Lancashire that the likes of Amazon, Starbucks and Google, which avoided paying corporation tax, lacked "moral scruples".
Last month the House of Commons Public Accounts Committee issued a report accusing Starbucks, Amazon and Google of "immorally minimising their tax obligations" in the UK by funnelling earnings offshore.
"We've got to crack that (tax evasion by multinationals), you're absolutely right," Cameron said in response to a businessman's question about why big foreign companies have been allowed to get away with paying next to nothing in tax.
"This is a really important issue. I think we're actually offering a fair deal to businesses. We're saying, 'Look, we're going to have a really low rate of corporation tax' but I want to make damn sure that those companies pay it.
"It's simply not fair and not right what some of them are doing by saying, 'I've got lots of sales here in the UK but I'm going to pay a sort of royalty fee to another company that I own in another country that has some special tax dispensation'."
Mr Cameron said he had put it "at the top of the agenda" for the G8, as well as tackling it nationally.
He says a crackdown can only be effective if countries around the world act collectively. Britain, along with France and Germany has asked the Organisation for Economic Cooperation and Development to look into whether tax loopholes can be closed.
Mr Cameron called for a crackdown on aggressive tax avoidance in a letter to other leaders of the G8 nations earlier this week.