The air base is near the city of al-Bukamal, where Daesh took control in 2014. The city is one of the main transit points used between Syria and Iraq by Daesh.
Rebel fighters recently began taking territory surrounding al-Bukamal, including militant-held positions.
The US-backed New Syria Army on Tuesday began efforts seeking to cut off Daesh's transit between Syria and Iraq. Several rebel factions have taken part in the operation.
The New Syrian Army seized control of the airbase on Wednesday but continued clashes with the militants forced the rebels to retreat.
"More than 40 rebel fighters were killed in the ISIS offensive on Hamdan airport," a spokesman for the New Syrian Army told ARA News. "Our forces retreated to avoid further losses, as the ISIS radical group brought huge military reinforcements to the area."
Syria has been blighted by a complex civil war in which Daesh, the Syrian government and multiple Syrian rebel groups fight for control of territory.
In Iraq, the Iraqi security forces recently took back control of the city of Fallujah. Iraqi forces are continuing efforts to take the city of Mosul, Iraq's second-largest city, away from Daesh control.
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