Such fighting would "cause even more insecurity and suffering," Blinken told reporters in Doha, Qatar, alongside Qatari Prime Minister Mohammed bin Abdulrahman Al Thani.
Blinken was roughly halfway through a nine-stop tour around the Middle East, his fourth diplomatic mission since the war began after Hamas' Oct. 7 terror attack on Israel killed 1,200.
Blinken has more meetings with Arab leaders in the United Arab Emirates and Saudi Arabia before heading to Israel and Egypt. De-escalation, he said, "is at the heart" of these discussions amid repeated altercations in the Red Sea, at the Israeli-Lebanese border and in Iraq and Syria.
US officials have said militant groups like Hezbollah and the Houthis, in Lebanon and Yemen, as well as Iranian-backed proxy fighters, are behind some of the incidents.
Looking ahead to his meetings with Israeli leaders in Tel Aviv and the West Bank set for early this week, Blinken said Sunday, "I will also raise the imperative of doing more to prevent civilian casualties. Far too many Palestinians, innocent Palestinians, have already been killed."
The secretary of state, like other US officials including President Joe Biden, have sought to stress their support for Israel's retaliatory operations against Hamas while calling for Israel to do as much as possible to curb civilian casualties in light of the ongoing onslaught in Gaza and high death toll.
The Israeli military insists it takes steps to avoid attacking non-Hamas fighters, and Israeli officials often say that Hamas embeds itself in civilian infrastructure, essentially using it as a shield, in violation of international law.
The death toll in Gaza surpassed 22,800 as of Sunday, according to the Palestinian Ministry of Health, amid repeated calls from Arab leaders for a broad cease-fire, including from Al Thani, who's also the Qatari minister for foreign affairs and a key figure in negotiations over freeing the more than 100 hostages thought to still be held in Gaza.
Blinken said Sunday that he was "grateful" to the Qataris for their "instrumental" help in the previous release of over 100 hostages that went along with a pause in fighting in November. Blinken has repeatedly said his diplomacy is focused on improving humanitarian conditions in Gaza and freeing hostages.
He stood at odds with his Qatari counterpart over the need for a cease-fire but signaled Israel's military should reconsider its approach.
"I think it's also very, very important that, to the extent operations continue, they be designed around protecting civilians and around getting humanitarian assistance people need, not the other way around," the secretary said. The UN humanitarian chief on Friday said Gaza has become "uninhabitable" after three months of fighting and Israeli bombardment aimed at Hamas.
"People are facing the highest levels of food insecurity ever recorded [and] famine is around the corner," said Martin Griffiths, the UN undersecretary-general for humanitarian affairs.
Blinken told reporters in Qatar that he learned the figure of food insecure people in Gaza was as high as 90%.
He reiterated that the US opposed to the permanent displacement of Gazans, a proposal embraced by hard-line members of Israel's right-wing government.
"Palestinian civilians must be able to return home as soon as conditions allow. They cannot, they must not, be pressed to leave Gaza," Blinken said.
He called the words of some Israeli ministers and lawmakers "irresponsible" and "inflammatory" and said the UN has a "crucial role" to play in resettling displaced Palestinians.
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