An Assad regime bombardment struck a building in farmland near the town of Dana used as a supply station for diesel fuel, the Syrian Observatory for Human Rights (SOHR) said.
Large numbers of first responders attempted to extinguish flames that sent massive plumes of black smoke billowing into the sky.
The depot is owned by a fuel company affiliated with authorities in Idlib, who are backed by Hayat Tahrir al-Sham, the Britain-based SOHR said.
A previous shelling by the Assad regime on February 12 resulted in the killing of six civilians, including women and children.
The shell fell on a civilian home and wounded many others.
The Assad regime and its ally Russia have regularly targeted hospitals and civilian areas since the start of the war in 2011.
Despite a ceasefire deal reached in March 2020 between Turkey and Russia, Damascus has intensified attacks on southern Idlib since June.
The war in Syria has killed around half a million people and displaced millions more.