Opuntia setispina is a species of cactus found in the Sierra Madre Occidental in Chihuahua, Sonora, and Durango in Mexico. The name O. setispina has been listed as a synonym under Opuntia macrorhiza and Opuntia pottsii, but shows no close relationship to either species. It is more of a woody shrubby, often somewhat tree-like species, growing up to approximately 1 meter tall and wide. It is morphologically similar to Opuntia chlorotica, Opuntia santa-rita, and Opuntia gosseliniana.

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