State news agency SANA said the blast wounded more than 100 people while the Britain-based Syrian Observatory for Human Rights said dozens were hurt.
The Observatory said an army colonel, a policeman and woman were among the 16 killed in Homs. Homs Governor Talal Barazzi said most of the 16 dead were women and children, adding that 15 of the wounded were treated at hospitals and released.
Today's blast came a few days after hundreds of rebels and their families left Waer, the last opposition-held neighbourhood of Homs, as part of a local truce that will bolster government control of the city.
SANA and the Observatory said the blast occurred near a hospital in the Zahra neighborhood. SANA added the car that exploded was rigged with some 150 kilograms of TNT and that shortly after the blast, a gas cylinder blew up in one of the nearby shops and wounded several policemen.
In northern Syria, the Observatory and the Local Coordination Committees, another opposition group that tracks the country's civil war, said Russian airstrikes hit the rebel-held town of Atareb.
The Observatory said 10 were killed in the airstrikes while the LCC said four were killed.
Russia has been one of the strongest supporters of Syrian President Bashar Assad since the start of the crisis in March 2011.
Syria's civil war has killed more than 250,000 people and wounded a million.
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