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Di Franco (also spelled DiFranco) is a surname. Notable people with the surname include:
- Ani DiFranco (born 1970), American-Canadian singer-songwriter
- Doug DiFranco, American hip hop producer from the duo Double Dee and Steinski
- Francisco Di Franco (born 1995), Argentine professional footballer
- Gianluigi Di Franco (1953–2005), Italian singer
- Giovanni Cola di Franco (fl. early 1600), Italian Mannerist architect
- Loretta Di Franco (born 1942), American operatic soprano
- Luigi Di Franco (1918–?), Italian footballer