"Slayer is devastated to inform that their bandmate and brother, Jeff Hanneman, passed away at about 11 a.m. [Thursday] near his Southern California home," the statement said.
"He is survived by his wife Kathy, his sister Kathy and his brothers Michael and Larry, and will be sorely missed," the website statement said.
The guitarist, a founding Slayer member who said he was influenced by punk music growing up, contributed lyrical and musical material to every Slayer album since the group's 1981 founding.
Slayer, which rose to mainstream fame with its 1986 album "Reign in Blood," is widely considered one of the "Big Four" thrash metal acts, along with Metallica, Megadeth and Anthrax.
Hanneman co-wrote Slayer songs "Raining Blood," "War Ensemble," "South of Heaven," "Seasons in the Abyss" and "Angel of Death," which are played at almost every live Slayer show.
The group won its first Grammy Award in 2006 for Best Metal Performance for "Eyes of The Insane." It earned the same award in 2007 for "Final Six," joining Metallica as the only band to win the category in consecutive years.
"Jeff Hanneman will always be a metal god," wrote multi-instrumentalist rocker Andrew W.K., known for the 2001 hit single "Party Hard." "A true master, he gave energy and excitement to millions, and will continue to. #PartyForSlayer."
Hanneman withdrew from touring in early 2011 after he contracted necrotizing fasciitis, which music magazine Billboard reported most likely came from a spider bite. The quick-progressing infection eats away at the flesh from deep layers of skin and tissue.
Bassist-vocalist band member Tom Araya said last year Hanneman had recovered, but lead and rhythm guitarist Kery King said three months ago continuing health problems kept Hannamen from working.
It was not immediately known if the skin ailment was connected to Hanneman's liver failure.