The effect of size of Pt nanoparticles has an important influence on the performance of supported Pt-based catalysts for the elimination of toluene. Herein, uniform Pt nanoparticles with average sizes of 1.5, 2.0, 2.5, 2.9, and 3.6 nm were obtained and supported on manganese oxide octahedral molecular sieves (OMS-2), and their catalytic performances for toluene oxidation were evaluated. Benefiting from the moderate interfacial interaction between nanoparticles and manganese oxide support, Pt/OMS-2-3 with the Pt particle size of 3.0 nm showed the best catalytic performance owing to the highest content of Pt2+ species. It also facilitates the formation of more abundant Mnδ+ (Mn2+ and Mn3+) and oxygen vacancies than that of the other sizes of the OMS-2-supported Pt nanoparticles, which can be filled by a large amount of adsorbed oxygen and converted into reactive oxygen species. We further showed that the resulting surface synergetic oxygen vacancies (Pt2+-Ov-Mnδ+) play a decisive part in catalyzing the complete oxidation of toluene. The result will provide new insights for designing efficient Pt-based catalysts for deep purification of toluene.