The escalating cycle of reprisals between the United States and Iran is threatening the delivery of aid to millions across the Middle East, the Norwegian Refugee Council warned Wednesday.

"Tens of millions of people across the Middle East need humanitarian assistance. Most of them are already devastated or displaced by conflict," NRC chief Jan Egeland said in a statement.

"Another confrontation among international and regional powers would be deadly for aid lifelines on the brink of collapse," he warned.

The killing last week in a US strike in Baghdad of top Iranian commander Qasem Soleimani has touched off a bloody cycle of tit-for-tat violence between the two foes.

Iran responded by firing missiles on a US air base in western Iraq overnight. Each side has warned the other that any new attack would trigger a fierce response.

The escalation has raised fears of a major conflict engulfing the entire region, across much of which the arch-foes and their proxies have a military presence.

"24 million war-affected Yemenis and 12 million Syrians displaced within the region are extremely vulnerable to any escalation in conflict, sanctions or restrictions on movement," Egeland said.

Egeland, whose organisation is one of the world's leading aid groups, also mentioned the plight of six million people in Iraq, two million people in the occupied Palestinian territories, and three million Afghan refugees in Iran who are in need of humanitarian assistance.

"On behalf of the millions in need that have nothing to do with the political conflict, we urge de-escalation of this confrontation and direct talks among diplomats to find solutions," Egeland said.

"Do not make a difficult situation impossible," he said.