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8 year oldShe will leave the AOL-owned site to run a new venture, Thrive Global, she said on her Twitter feed.
"I thought HuffPost would be my last act. But I've decided to step down as HuffPost's editor-in-chief to run my new venture, Thrive Global," she said.
Thrive Global is described as a project designed to combat workplace "burnout".
In a media release, Ms Huffington, 66, says it is "a corporate and consumer well-being and productivity platform".
Across all nine international Huffington Post sites, there are 81m monthly unique visitors. It launched its UK edition in 2011.
Tim Armstrong, AOL chief executive, said that thanks to Arianna, the Huffington Post was a "firmly established and celebrated news source".
The Huffington Post was launched on 9 May, 2005, pulling together liberal-leaning news reports, and as an alternative to conservative news aggregators such as the Drudge Report.
She launched the site with the American businessman Kenneth Lerer and other investors.
The site offers news, blogs, and original features, and covers politics, lifestyle, and entertainment.
"The journey of the last 11 years has exceeded my wildest expectations," Ms Huffington said, referring to the HuffPost, as it is also known.
"When I decided to create Thrive Global, I thought it would be possible to build a start-up and continue as editor-in-chief of the Huffington Post. Today, it's clear that was an illusion," she added.
"As Thrive Global moved from an idea to a reality, with investors, staff, and offices, it became clear to me that I simply couldn't do justice to both companies. Change is desperately needed if another generation is to avoid the burnout that all too often comes with success today."
Arianna Huffington was born Arianna Stassinopoulos in Athens in 1950. She left her native country to study economics at Cambridge University, where she became president of the Cambridge Union.
She moved to America and in 1986 married Texas oil billionaire Michael Huffington. She played a major role in his election to the US House of Representatives in 1992 as a Republican candidate and in his failed bid for a Senate seat two years later.
By this point, Ms Huffington had made a name in her own right as a figure in the Republican establishment and a key supporter of Newt Gingrich and other right-wing figures.
But she left the party in 1996, and divorced her husband the following year, as she moved on a journey to the left.
In 2011, AOL acquired The Huffington Post for $315m, and made her president and editor-in-chief.
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