Women, children and UN staff were among the dead after a school where Palestinians were sheltering in Beit Hanoun, northern Gaza, was hit.
A spokeman for the Israeli government told Channel 4 News an Israeli shell “might have been” the cause of the deaths.
The Gaza health ministry said at least 15 people had been killed and 200 wounded. Israeli media reported that most of those killed at the UNWRA school were children.
Palestinians who had been sheltering in the school blamed the devastation on Israeli rockets, saying the Red Cross had told local people the school was safe.
The UN said it gave the Israeli military the precise co-ordinates of the school in order to avoid a strike.
Robert Turner, director of UNWRA operations in Gaza, Robert Turner, said: “This school was a designated emergency shelter, which meant that we had given the Israeli authorities, the IDF, the co-ordinates of this school on 12 separate occasions, most recently 10.56 this morning.
“They were fully aware that this was a shelter, we knew that the situation in Beit Hanoun was deteriorating from a security standpoint.
“So over the course of the day we had been trying to coordinate a window period during which we could withdraw our staff and any of the displaced who choose to go to a safe location would be able to leave. We were never confirmed that window, that time period.”
UN Secretary General Ban Ki Moon said he was appalled by the attack but the circumstances remained unclear.
Yigal Palmor, spokesman for the Israeli Ministry of Foreign Affairs, told Channel 4 News: “What we know is that this area, the area of the school, was a place where a Hamas anti-tank squad was active in these last few days.
“And we have warned UNWRA a couple of days ago to evacuate the premises, because Hamas has turned them into a battleground.
“So it might have been a response fire to Hamas anti-tank fire, or it might have been a Hamas mortar shell or rocket. We still don’t know at this point.”
Mr Palmor said pictures of the aftermath of the attack on the school were “horrendous and heartbreaking” but said Hamas had been stashing rockets at UN premises and were deliberately fighting in civilian areas.
The attack on the school means the death toll in Gaza reached 747 on Thursday. Israeli tank fire and pre-dawn assaults killed 35 people, including an 18-month-old baby and six members of the same family, Palestinian officials said.
Gaza militants continued to fire rockets at Israel on Thursday, sending thousands in the country’s south racing to shelters or safe rooms.