His death comes on the day members of his former team visit President Donald Trump at the White House to be commended for their Super Bowl victory over Atlanta in February.
Massachusetts Department of Correction said Hernandez had tried to block the door to his single cell before hanging himself.
Lifesaving techniques were performed on Hernandez and he was taken to UMASS Leominster hospital where he was pronounced dead at 04:07 local time (08:07 GMT).
State police are on the scene and his next of kin have been notified, officials said.
State Department of Correction spokesman Christopher Fallon said in a statement that he was not aware a suicide note had been written and that officials had not been concerned that Hernandez would take his life.