The facility, like almost all of Gaza's schools, has been used as a shelter for people who have been forced to flee their homes by the war.
The Israeli military acknowledged the early Saturday strike, claiming it hit a Hamas command centre within the school. Hamas denied that.
The strike hit without warning in the early morning before sunrise as people were praying at a mosque inside the school, according to Abu Anas, a witness who worked to rescue people. Many of the dead were unrecognisable, he said, adding that he expected the death toll to rise. Many of the casualties were women and children, he said.
Israel has blamed civilian deaths in Gaza on Hamas, saying the group endangers noncombatants by using schools and residential neighbourhoods as bases for operations and attacks. The strike came as American, Qatari and Egyptian mediators renewed their push for the two parties to achieve a cease-fire agreement that could help calm soaring tensions in the region following the assassination of top Hamas political leader Ismail Haniyeh in Tehran and a senior Hezbollah commander in Beirut.
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