Pt-Pd nanoparticles are structure-engineered by successive electroless deposition and galvanic displacement technique, to manifest a shell-core configuration. Based on the microscopic analysis, the nanoparticles present an uniform distribution. When applied as an electrocatalyst, they are confirmed to be highly active toward both methanol and ethanol oxidation reaction for a prolonged time. In addition, the catalyst is more resistive against CO-poisoning than conventional Pt catalyst. The stable activity of Pt-Pd catalyst is ascribed to the surface-tuned electronic property of Pt over-layer, which leads to a weak adsorption strength to CO and a high affinity to OH. The modified binding ability of surface Pt was reflected by CO-stripping experiment and by monitoring of electrochemical surface area over multiple times. The observed chemical stability of as-prepared catalyst is further proved and supplemented by a computational investigation via density functional theory calculation. The experimental and theoretical outcomes indicate that the catalyst is suitable and applicable for the direct methanol and ethanol oxidation in DAFC.