The 69-year-old star of the Hollywood hit Who Framed Roger Rabbit has enjoyed a career spanning four decades.
In a statement on Wednesday, his agent said he was withdrawing from acting after a "wonderful career" and would be spending time with his family.
Hoskins achieved a Golden Globe nomination for his role as a private detective opposite the animated bunny.
"He wishes to thank all the great and brilliant people he has worked with over the years, and all of his fans who have supported him during a wonderful career," said the statement.
"Bob is now looking forward to his retirement with his family, and would greatly appreciate that his privacy be respected at this time."
Hoskins, from Suffolk in England has played a wide variety of roles since the 1970s ranging from gritty gangster films to comedy roles.
He played Harold Shand in the 1980 British gangster film, The Long Good Friday alongside Helen Mirren.
His last screen appearance was in Snow White & The Huntsman, in which he played one of the seven dwarves opposite Kristen Stewart.
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