de la O is a surname of Spanish origin, and may refer to:
- Marco de la O (born 1978), Mexican actor
- Rogelio Ramírez de la O (born 1948), economist based in Mexico City
- Valentino de la O, host of the Val De La O Show
- Genovevo de la O (1876–1952), figure in the Mexican Revolution in Morelos
- María de la O Lejárraga García (1874–1974), Spanish feminist writer, dramatist, translator and politician, pseudonym María Martínez Sierra
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