de Soto is a Spanish surname. Notable people with the surname include:

• Alexander de Soto (1840–1936), Spanish American physician, businessman, and philanthropist
• Álvaro de Soto (born 1943), Peruvian diplomat and UN special envoy
• Domingo de Soto (1494–1560), Spanish theologian
• Ernest de Soto (1923 – 2014), American master printmaker and lithographer.
• Francisco de Soto (c. 1500–1563), Spanish organist and composer
• Hernando de Soto (c. 1496/1497–1542), Spanish conquistador
• Hernando de Soto Polar (born 1941), Peruvian economist and author
• Jesús Huerta de Soto (born 1956), economist of the Austrian school, born in Spain
• Luis Barahona de Soto (1548–1595), Spanish poet
• Pedro de Soto (1493–1563), Spanish theologian
• Benito de Soto (1805–1830), pirate
• Ernestine Ygnacio-De Soto, sometimes written as Ernestine Ygnacio De Soto, Barbareño Chumash activist and historian.