In a speech on Monday morning, the prime minister told backbenchers not to be seduced by a "stop the world, I want to get off" approach to politics.
"There are those who say we should turn our backs on the world and on our wider obligations, that we should cut ourselves off from influential organisations in the belief that we can go it alone," he said. "I know how appealing some of these arguments are but they amount to the same thing: denial."
In a speech setting out his vision of the UK's role in the world a week ahead of the G8 conference in Northern Ireland, Cameron insisted that continued membership of the EU was "in our national interest" and that it was important to be at the top table.
His characterisation of the anti-EU sentiment within the Conservative Party is likely to anger many in his own party.
Tory MEP Daniel Hannan mocked Cameron's assessment on Twitter: "A slip of the tongue, PM, easily done. I think you mean that British membership gives the EU a top table seat, not the other way around."
The prime minister restated his pledge of an in-out referendum on Britain's EU membership if the Tories win the general election.
But he made a strong argument for Britain's continued membership of a reformed EU as part of its interest in having an influence on world affairs.
"The particular nature of Britain - our economic interests, our cultural ties, our history, our businesses, our location, our very instincts, they combine to make ours a country that is not just on the map but truly in the world," said the Prime Minister.
"When your prosperity is won in far-flung places, when your fortunes are disproportionately affected by what happens beyond your borders, then your national interest is not just about standing up for yourself - but standing up for what's right, and standing for something more."