The actress died on Sunday morning at Cedars-Sinai Medical Center near Beverly Hills, a hospital spokeswoman has confirmed.
The LA Times said Murphy went into cardiac arrest, but hospital sources would not release the cause of death.
Murphy was married to British screenwriter Simon Monjack. The couple lived in Los Angeles.
Reports said the LA fire department responded to a medical call at Murphy's home in West Hollywood at 0800 local time (1600 GMT).
Two hours later, she was pronounced dead at hospital.
Murphy grew up in New Jersey but moved to Los Angeles with her mother to pursue acting.
She got her start in the sleeper hit Clueless and rose to stardom in 8 Mile alongside rapper Eminem.
Her on-screen roles declined in recent years, but Murphy voiced characters for the hit US television series, King of the Hill, and animated movie Happy Feet.
She is due to appear in Sylvester Stallone's film, The Expendables, set for release next year.
Murphy once dated Ashton Kutcher, who co-starred with her in the 2003 romantic comedy, Just Married.
Kutcher tweeted Sunday morning about Murphy's death: "2day the world lost a little piece of sunshine."
"My deepest condolences go out 2 Brittany's family, her husband, & her amazing mother Sharon," his tweet said.
Source: BBC News
Another shocking death, we've lost so many great entertainers this year (all well before their time).
Brittany's talent has always been very underrated I think, but I've always liked her. Clueless remains one of my faves till this day.
My deepest sympathies go out to her family and friends.
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