Rational design of the durable catalysts is an important issue for improving the application performance of synthesized electrocatalysts for methanol oxidation reaction (MOR). In this work, mesoporous Pd6Ru4/TiO2-1 composite catalyst is prepared by using two-step reaction. Compared with 20%Pd/C, PdRu, Ru/TiO2-1, and Pd/TiO2-1 catalysts, Pd6Ru4/TiO2-1 catalyst has several merits of abundant electrochemical surface areas, excellent electrocatalytic activity and long-term-use stability. Ru doping into Pd/TiO2-1 greatly optimizes the electronic structure of Pd by decreasing its electron density. Pd6Ru4/TiO2-1 also exhibits high turnover number (TON), low activation energy (ΔEa) values for MOR, and higher tolerance to CO-poisoning. A satisfactory level of methanol conversion to the final products is validated by chromatographic results. Density functional theory (DFT) calculation could deepen the understanding of excellent tolerance to CO-poisoning.