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South San Francisco is a city in San Mateo County, California, United States, located on the San Francisco Peninsula in the San Francisco Bay Area. The population was 63,632 at the 2010 census.

South San Francisco lies north of San Bruno and San Francisco International Airport in a small valley south of Daly City, Colma, Brisbane, and San Bruno Mountain, east of Pacifica and the hills of the Coast Range, and west of the waters of San Francisco Bay. Locals often refer to the town as "South City," in much the same way that San Francisco is called "The City." People unfamiliar with the area often mistake "South San Francisco" as the southern part of the city of San Francisco. In fact, the city of South San Francisco is not even contiguous with the city of San Francisco, due to the city of Brisbane being between them.

Most of the valley faces San Francisco Bay, affording bay views from higher levels. South San Francisco has mild winters and dry cool summers. The hills to the west shield the city from much of the fog that prevails in neighboring areas.

The population has tripled since World War II with the opening of such subdivisions as Buri Buri, Winston Manor and Westborough on the slopes west of El Camino. It has grown from 4,411 in 1920 to 61,824 in 2006. As of the last Census and the published results in 2011, the population of South San Francisco stands at 64,409.

The city is noted for the South San Francisco Hillside Sign on Sign Hill, which rises to the north of the city, with large white letters that proclaim "South San Francisco, The Industrial City". The sign, a tribute to the city's industrial past, is listed on the National Register of Historic Places.