Australia team doctor Peter Brukner said he never regained consciousness and died in hospital in Sydney.
Hughes, 25, was carried off on a stretcher at the Sydney Cricket Ground after a short-pitched delivery struck his head, missing his helmet.
He had CPR and mouth-to-mouth resuscitation before being taken to hospital and placed in an induced coma.
In a statement, Peter Brukner said: "It is my sad duty to inform you that a short time ago Phillip Hughes passed away. He never regained consciousness following his injury on Tuesday.
"He was not in pain before he passed and was surrounded by his family and close friends.
"As a cricket community we mourn his loss and extend our deepest sympathies to Phillip's family and friends at this incredibly sad time.
"Cricket Australia kindly asks that the privacy of the Hughes family, players and staff be respected."