Pt/CeO 2 catalysts exhibit excellent catalytic performance for the methanol dehydrogenation (MD) reaction. In this work, MD reactions on three systems of Pt 1 /CeO 2 (110)), Pt 7 /CeO 2 (110), and Pt 1 /Ce 1- x O 2 (110) are investigated via density functional theory (DFT) calculations. The CH 3 OH adsorption, electronic structure of the catalyst, and mechanism of methanol decomposition (MD) are systematically calculated. The results reveal that the d-band center of the Pt atom moves away from the Fermi level in the order of Pt 1 /CeO 2 (110) < Pt 7 /CeO 2 (110) < Pt 1 /Ce 1- x O 2 (110), and the order of the activity of the MD reaction is Pt 1 /CeO 2 (110) < Pt 7 /CeO 2 ( 1 10) < Pt 1 /Ce 1- x O 2 (110). The results of the microkinetic dynamics simulation verify that only Pt 1 /Ce 1- x O 2 (110) is conducive to the decomposition of methanol at low temperatures (373 K), and the products CO and H 2 are easily dissociated from the catalyst surface. This work uncovers that both the small size and the Ce vacancy substituted sites of Pt favor the performance of the Pt/CeO 2 catalyst, and provides theoretical guidance for the construction and design of efficient metal-support catalysts for the MD reaction.