Metal support interactions modulation is one of the effective strategies to enhance the catalytic performance. Herein, we reported that modulating metal support interactions by switching the strength (CO, H2, NH3) and temperature (200, 300, 400 °C) of reducing gases is a facile way to improve the catalytic performance of Pt/CeO2 for toluene oxidation. The distinct reduction treatments will stepwise enhance the reducibility, ratio of Pt0 and oxygen vacancy concentration, which dominated the activity. The metal support interactions modulation can significantly affect toluene deep oxidation (from benzoate to formate or monodentate carbonate) via enhancing the mobility of surface/lattice oxygen and activation ability towards O2 molecules, since the main activation sites for O2 molecules expand from Pt0 sites to oxygen vacancies and Pt0 sites with temperature increasing.