Regulating the metal–support interaction (MSI) of supported metal catalysts is critical to enhancing their catalytic performance. However, achieving direct control over the MSI by tuning the properties of irreducible oxide-supported supports remains a challenging task. In this study, we propose a surface modification strategy to refine the MSI on an irreducible MgAl2O4-supported Pt catalyst. By employing a facile H2O2 treatment to modify the support surface, the number of Brønsted acid sites on MgAl2O4 was successfully reduced. The MSI between Pt and MgAl2O4 is appropriately weakened, resulting in a higher proportion of metallic Pt species, while maintaining a high level of dispersion during the reaction. These metallic Pt species enhance the activation ability of C–H bonds in propane and facilitate the rapid consumption of intermediate species. Consequently, the complete propane oxidation reaction performance of H2O2-treated Pt/MgAl2O4 is significantly promoted, exhibiting an impressive increase in intrinsic activity of over 32-fold compared to traditional Pt/MgAl2O4.