The attack targeted the Imam Ali bin Abi Talib Mosque in the Wadi al-Dahab neighborhood of Homs shortly after Friday prayers, the Syrian Arab News Agency (SANA) reported.
State media said security forces had imposed a cordon around the area and were investigating.
Local officials said it may have been caused by a suicide bomber or explosives placed there.
Al Jazeera’s correspondent in Aleppo said that Homs is home to a diverse population of Alawites, Christians and Sunni Muslims, adding that the attack targeted an Alawite mosque and warning it could “inflame sectarian tensions” across the country.
No group has claimed responsibility for the strike.
Last week the US bombed ISIL positions in Syria in retaliation for the killings of two US soldiers and a civilian interpreter. Damascus also joined a global anti-ISIL alliance in November, vowing to crush the remaining elements of the group.
Friday’s attack underscores Syria’s fragile security situation, as the new authorities in Damascus struggle to assert control.