Alfie Evans, the 23-month-old toddler at the centre of a High Court legal battle, has died, nearly a week after his life support was withdrawn.
The boy from Merseyside, who had a degenerative brain condition, died at 02:30 BST, his father Tom Evans said.
On Facebook he wrote: "My gladiator lay down his shield and gained his wings... absolutely heartbroken."
Alfie's parents lost legal challenges against a High Court ruling allowing the hospital to withdraw ventilation.
The boy had his life support withdrawn on Monday after being in a semi-vegetative state for more than a year.
Mr Evans and Alfie's mother Kate James's legal campaign attracted widespread media attention and saw them clash with doctors over the child's treatment.
A statement from Alder Hey Children's Hospital in Liverpool, where Alfie was treated, said staff expressed their "heartfelt sympathy".
"All of us feel deeply for Alfie, Kate, Tom and his whole family and our thoughts are with them. This has been a devastating journey for them."
Alfie, who was born in May 2016, was first admitted to Alder Hey hospital the following December after suffering seizures, and had been a patient at the hospital ever since.
The parents, who lived in Bootle, wanted to fly the toddler to a hospital in Italy for treatment, but this was rejected by doctors who said continuing treatment was "not in Alfie's best interests".
The hospital said scans showed "catastrophic degradation of his brain tissue" and that further treatment was not only "futile" but also "unkind and inhumane".
The court battle between the parents and medical staff lasted for four months.
The couple heavily criticised medical staff, with Mr Evans suggesting his son was a "prisoner" at the hospital and had been misdiagnosed.
The High Court ruled in favour of hospital bosses on 20 February, after accepting medical evidence that there was "no hope" for the youngster.
The parents contested the ruling, but the Court of Appeal upheld it, and attempts to argue the case at the Supreme Court and the European Court of Human Rights (ECHR) were rejected.
Alfie's case brought swathes of international support including from Pope Francis, who tweeted support for the family and asked that "their desire to seek new forms of treatment may be granted".
Earlier in April Mr Evans visited Pope Francis in Rome, pleading with him to "save our son".
Alfie was granted Italian citizenship on Monday, with the country's ministry of foreign affairs saying it hoped the ill toddler would be allowed an "immediate transfer to Italy".
Alfie's parents then began a further appeal against the order stopping them from taking him to Italy, which was heard on Wednesday afternoon by a panel of three Court of Appeal judges, headed by Sir Andrew McFarlane.
The judges upheld a ruling preventing the 23-month-old from travelling abroad after life support was withdrawn.
Supporters of Alfie's parents held protests outside the hospital, prompting its bosses to defend staff who they said had endured a "barrage" of abuse.
On Monday a group of protesters tried to get into Alder Hey hospital after the ECHR refused to intervene in the case.
Merseyside Police is investigating claims patients and staff were intimidated.
On Thursday, Mr Evans thanked supporters of Alfie's case, known as Alfie's Army, but asked them "to go home" so the parents could build a relationship with the hospital to come up with a plan "that provides our boy with the dignity and comfort he needs".