Oxygen vacancies can change the physical and chemical properties of oxide semiconductors, which is applied to the field of ph otocatalysis, including water splitting, carbon dioxide reduction, and organic synthesis. However, the mechanism of oxygen vacancies in photocatalytic organic synthesis is still unclear. Herein, oxygen vacancies constructed on spinel CuFe2O4 nanoparticles were found to trigger the photocatalytic synthesis of an unsaturated amide with high conversion and selectivity. Such superior performance was attributed to the fact that the enriched surface oxygen vacancies could increase the charge separation efficiency and optimize the reaction path, which has been demonstrated both experimentally and theoretically.