The blast went off at the entrance of Hillah city during morning rush hour as dozens of cars were waiting to be searched. Thirteen civilians, including a woman and 12-year old child, and nine security personnel were killed, two police officers said. At least 55 other people were wounded, they said.
Police say the victims' burns suggested the bomber packed his car with liquid fuel, probably gasoline.
The Shiite-dominated city is located about 60 miles (95 kilometers) south of Baghdad.
Two medical officials confirmed the figures. All officials spoke on condition of anonymity as they were not authorized to release information.
Iraq has seen a spike in violence since last April, with the death toll climbing to its highest levels since the worst of the country's sectarian bloodletting in 2006-2008. The UN says 8,868 people were killed in 2013, and more than 1,400 people were killed in January and February of this year.
No one immediately claimed responsibility for the attacks, but they bore the hallmarks of an al-Qaida breakaway group that frequently uses car bombs and suicide attacks to target public areas and government buildings in their bid to undermine confidence in the government.