The hospital is located underground, a tactic used by the opposition to avoid targeting in the conflict-prone area.
The explosion killed at least five civilians, including a child and a woman, and injured medical staff, according to the Syrian Civil Defence volunteers, known as the White Helmets.
A video posted on the local health directorate’s Facebook page showed debris and blood stains at the entrance of the hospital.
Fadi Hakim, a spokesman for the Syrian American Medical Society, which supports the hospital, said the structural damage includes destruction of the orthopaedic clinic and the emergency room.
Attacks on hospitals are common in the Syria conflict, and are mostly blamed on government and allied forces. The health directorate in the rebel-controlled north-west said the attack on Sunday was the first on a medical facility in the region since February 2020.
The US-based Physicians for Human Rights has documented 598 attacks on at least 350 separate healthcare facilities in Syria since March 2011, the vast majority of them allegedly committed by the Syrian government and allied forces, including Russia.
In the same 10-year period, at least 930 medical personnel were killed, the rights group said.
The government views rebel-held areas as controlled by terrorists.