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In this paper, we report the synthesis, characterization, and electrochemical evaluation of a mesoporous PtSnO2/C catalyst, called PtSnO2(M)/C, with a nominal Pt : Sn ratio of 3 : 1. Brunauer–Emmett–Teller and transmission electron microscopy characterizations showed the obvious mesoporous structure of SnO2 in PtSnO2(M)/C catalyst. X-ray photoelectron spectroscopy analysis exhibited the interaction between Pt and mesoporous SnO2. Compared with Pt/C and commercial PtSnO2/C catalysts, PtSnO2(M)/C catalyst has a lower active site, but higher catalytic activity for ethanol electro-oxidation reaction (EOR). The enhanced activity could be attributed to Pt nanoparticles deposited on mesoporous SnO2 that could decrease the amount of poisonous intermediates produced during EOR by the interaction between Pt and mesoporous SnO2.