The one-time New England Patriots tight-end was discovered hanging in his cell at the Souza Baranowski Correctional Center in Shirley, Massachusetts, at approximately 3.05am local time.
His suicide comes just days after he was acquitted of murdering two men in Boston in 2012.
"Mr. Hernandez was in a single cell in a general population unit," a statement by the Department of Correction said.
"Mr. Hernandez hanged himself utilizing a bedsheet that he attached to his cell window. Mr. Hernandez also attempted to block his door from the inside by jamming the door with various items."
Hernandez, 27, was taken to UMASS Leominster, where he was pronounced dead at 4.