Vanity Fair's website reported that he died at the MD Anderson Cancer Centre in Houston, Texas, surrounded by friends, whom he described this year as "my chief consolation in this year of living dyingly". He wrote last year that "cancer victimhood contains a permanent temptation to be self-centered and even solipsistic".
Hitchens was known for his heroic intake of alcohol and cigarettes. He wrote in 2003 that his daily intake of alcohol was enough to "stun the average mule".
He said he had given up smoking in 2008, but journalist and author Peter FitzSimons, who interviewed him for his appearance at the 2010 Sydney Writers' Festival, said Hitchens had still been smoking as of last year.
Hitchens was a columnist for Vanity Fair and online magazine Slate and the author of The New York Times bestselling book God is Not Great.
His most recent book was Arguably, a collection of his essays.
He was a famous iconoclast and wrote critically of Mother Teresa, Bill Clinton and Winston Churchill.
Hitchens took a third-class degree in philosophy, politics and economics from Oxford, where he was a contemporary of Mr Clinton.
He later wrote about his gay experiences at Oxford in Hitch-22, including a dalliance with two unnamed future members of Margaret Thatcher's cabinet.
He left university and joined the Times Higher Education Supplement but was fired within six months, and went on to write for New Statesman magazine, working alongside novelists Julian Barnes, Martin Amis and Ian McEwan.
His brother Peter is a conservative columnist for the the Daily Mail in London.
- with James Robertson