US Secretary of State Antony Blinken headed back to the Middle East Thursday on his fourth trip since the Israel-Hamas war began, expecting tough talks as he presses for immediate new aid for battered Gaza and regional de-escalation.

The top American diplomat will visit both Israel and the West Bank, home of the Palestinian Authority, and five Arab countries — Egypt, Jordan, Qatar, Saudi Arabia, and the United Arab Emirates, the State Department said.

Blinken departed late Thursday bound first for Turkey — an uneasy US ally that is the home of key Hamas leaders despite being one of the few Muslim-majority countries to recognize Israel — followed by Greece.

He will discuss "immediate measures to increase substantially humanitarian assistance to Gaza," where the World Health Organization has warned of the risk of famine and disease.

"We don't expect every conversation on this trip to be easy. There are obviously tough issues facing the region and difficult choices ahead," State Department spokesman Matthew Miller told reporters.

"But the secretary believes it is the responsibility of the United States of America to lead diplomatic efforts to tackle those challenges head-on," he said.

Blinken on previous trips sought to keep the war isolated to Gaza. But he returns to a region that has seen attacks in or from Lebanon, Iraq, Yemen, Syria, and Iran.

A strike inside Lebanon widely assumed to have been carried out by Israel killed a top Hamas leader on Tuesday, and Iran-backed Huthi rebels have been firing on ships in the Red Sea in avowed solidarity with Gaza.

In a pre-trip telephone call, Blinken agreed with French Foreign Minister Catherine Colonna to seek to "de-escalate tensions in the West Bank and to avoid escalation in Lebanon and Iran," the State Department said.

Iran was hit Wednesday by one of the deadliest attacks since its 1979 Islamic revolution, with twin blasts killing at least 84 people gathered to commemorate a slain Revolutionary Guards general. 

Tehran initially blamed Israel and the United States, although the Islamic State group later claimed responsibility and US officials rejected any US or Israeli role.