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The movie, which sees the return of actor Ron Perlman as the red-skinned hero, took $35.9m (Ј18.1m) on its opening weekend.
It nudged fellow superhero film Hancock into second place with $33m (Ј16.6m).
Opening at number three with $20.6m (Ј10.4m) was 3D adventure Journey to the Center of the Earth - the latest adaptation of Jules Verne's novel.
Mexican-born director Guillermo del Toro returned to direct the Hellboy sequel.
The original Hellboy movie also topped the North American box office in 2004 and went on to enjoy strong DVD sales.
Paul Dergarabedian, president of box office analysts Media By Numbers, said del Toro's acclaimed fantasy Pan's Labyrinth - which won three Oscars and three Baftas in 2007 - had "made a big impression on a lot of people".
"If they weren't fans of Guillermo del Toro before, they certainly are now," he added.
Disney animation Wall-E, the tale of a trash-compacting robot with a heart of gold, fell from number two to number four.
Wanted, starring James McAvoy and Angelina Jolie as members of a fraternity of assassins, fell from number three to number five.
Eddie Murphy's Meet Dave - a comedy about mini aliens operating a human - took just $5.3m (Ј2.7m) to make its debut in seventh place on its opening weekend.
(BBC)
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