The 27-year-old former New England Patriots tight end hanged himself with a bed sheet attached to a window in his cell at the Souza Baranowski prison in Shirley, the Massachusetts Department of Correction said. His body was discovered at 3:05 a.m.
Hernandez, who was alone in his cell in a general population wing, hanged himself and had "attempted to block his door from the inside by jamming the door with various items," the statement reads.
The Massachusetts State Police are investigating his death.
Hernandez was serving a life sentence after being convicted of first-degree murder for the June 2013 killing of Odin Lloyd, a semi-pro football player who was dating the sister of Hernandez's fiancée.
And until last week, he had been facing murder charges in the July 2012 deaths of Safiro Furtado and Daniel de Abreu, two men killed in a drive-by shooting outside a Boston nightclub.
But Hernandez was found not guilty Friday of two counts of murder in that case, though he was convicted of illegal possession of a firearm.
Hernandez was visibly emotional when Friday's verdicts were read, embracing his attorneys with tears in his eyes. One of his attorneys said Hernandez was relieved about the verdict.
Hernandez's attorneys had appealed for a new trial in the Lloyd case.
Hernandez had a promising football career before his June 2013 arrest in Lloyd's death. The Patriots' fourth-round pick in 2010 had signed a five-year contract extension in 2012 worth up to $40 million.
A jogger found Lloyd's gunshot-riddled body in a Massachusetts industrial park on June 17, 2013. Hernandez was charged with murder nine days later, and the Patriots released him.
Hernandez's death comes on the day his former team is set to visit the White House to celebrate its February Super Bowl victory.