Israel killed three of senior Hamas leader Ismail Haniyeh's sons in the Gaza Strip on Wednesday
The bombing, which targeted a civilian vehicle in north Gaza's Al-Shati refugee camp, also killed several of his grandchildren, the Al-Jazeera news network reported.
There were at least five people killed, Al-Jazeera journalist Ismail Al-Ghoul said.
"There is no doubt that this criminal enemy is driven by the spirit of revenge and the spirit of murder and bloodshed, and it does not observe any standards or laws," Haniyeh, who lives in Qatar, told Al Jazeera.
"We've seen it violate everything on the land of Gaza. There is a war of ethnic cleansing and genocide. There is mass displacement."
Attacks on Palestinian leaders' families and homes would not see them give in, Haniyeh added.
The head of Hamas's political wing said he had lost 60 family members following the outbreak of the Gaza war.
He said his sons had been travelling to Al-Shati camp seeing relatives for Eid Al-Fitr, the Islamic holiday marking the end of the fasting month of Ramadan.
Al-Jazeera said an Israeli drone fired a missile at the car carrying them and only one person was left alive – a wounded girl who was taken to a hospital.
The three children Haniyeh lost on Wednesday were named as Amir, Hazem, and Mohammad. Their killing comes amid a renewed push for a ceasefire in Gaza.
There was no respite for Palestinians during Ramadan, even though the UN Security Council demanded a ceasefire for the holy month.
The brutal Israeli war on Gaza continued on Wednesday, even as the strip's overwhelmingly Muslim population marked Eid.
Israel's military campaign has killed nearly 33,500 people and injured more than 76,000, according to the enclave's health ministry.
The International Court of Justice said in January that Israel was plausibly breaching the UN's Genocide Convention in the strip.