After missiles were fired from Gaza into Israel, Israel launched airstrikes against insurgent targets in the territory.
The Palestinian health ministry in Gaza, which is run by Hamas, reported that 20 people, including teenagers, had died as a result of the strikes.
As sirens wailed, Israel’s parliament in Jerusalem was evacuated due to missile fire.
In recent days, tensions between Israel and the Palestinians have risen dramatically.
After hundreds of Palestinians were wounded in clashes with Israeli police in Jerusalem on Monday, Gaza’s Hamas rulers vowed to strike.
Israel claimed to have assassinated at least three Hamas militants. “We have begun, and I quote, begun, to strike strategic targets in Gaza,” Lt Col Jonathan Conricus, an Israeli military spokesman, told reporters.
According to Hamas accounts, Mohammed Abdullah Fayyad, leader of the Izzedine al-Qassam Brigades, was killed.
Israel’s Prime Minister Benjamin Netanyahu said Hamas had “crossed a red line” and that Israel would respond “with great force”.
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US Secretary of State Antony Blinken said Hamas’ missile attacks would stop “immediately,” adding that “both sides must de-escalate.”
More than 300 Palestinians were injured in clashes with Israeli police outside the al-Aqsa mosque on Monday, in the worst unrest in Jerusalem in years.