The man cops say is responsible for Tupac Shakur's death was involved in a jailhouse brawl while awaiting trial in his 2Pac murder case ... and now he's facing a new charge.

Duane "Keefe D" Davis got into a physical fight with a fellow inmate at Clark County Detention Center in Las Vegas ... according to multiple reports.

Keefe D and his opponent engaged in "mutual combat by grappling and throwing closed fist strikes" ... and Keefe D allegedly put the other guy in a headlock.

Sounds like the fight was pretty intense ... reports say the two men were only separated after a corrections officer doused both inmates with pepper-spray.

Keefe D is now charged with battery by a prisoner, according to new legal docs obtained by TMZ. An officer reportedly says Keefe D told them he was "just standing his ground."

Tupac's alleged killer has been in custody in Sin City since September 2023, when he was indicted for the late rapper's murder ... the first big break in the cold case for a long, long time.

Keefe D's murder trial isn't set to begin until March ... he's pleaded not guilty.