AbstractThe efficiency of direct methanol fuel cell (DMFC) is largely determined by the activity and durability of methanol oxidation reaction (MOR) catalysts. Herein, we present a CO‐resilient MOR catalyst of palladium‐tin nano‐alloy anchored on Se‐doped MXene (PdSn0.5/Se−Ti3C2) via a progressive one‐step electrochemical deposition strategy. MOR mass activity resulting from Pd/Se−Ti3C2 catalyst (1046.2 mA mg−1) is over 2‐fold larger than that of Pd/Ti3C2, suggesting that the introduction of Se atoms on MXene might accelerate the reaction kinetics. PdSn0.5/Se−Ti3C2 with Se‐doping progress of MXene and the cooperated Pd−Sn sites has a superior MOR mass activity (4762.8 mA mg−1), outperforming many other reported Pd‐based catalysts. Both experimental results and theoretical calculation reveal that boosted electron interaction of metal crystals with Se‐doped MXene and optimized distribution of Pd−Sn sites can modulate the d band center, reduce adsorption energies of CO* at Pd site and enhance OH* generation at Sn site, resulting in highly efficient removal of CO intermediates by reaction with neighboring OH species on adjacent Sn sites.