Recently, high-entropy alloy nanoparticles (HEA NPs) have aroused great interest globally with their unique electrochemical, catalytic, and mechanical properties, as well as diverse activity and multielement tunability for multi-step reactions. Herein, a facile low-temperature synthesis method at atmospheric pressure is employed to synthesize Pd-enriched-HEA-core and Pt-enriched-HEA-shell NPs with a single phase of face-centred cubic structure for promoting the oxidation of C1 and C2 alcohols. Interestingly, the lattice of both Pd-enriched-HEA-core and Pt-enriched-HEA-shell enlarge during the formation process of HEA, with tensile strains included in the core and shell of HEA. Strikingly, the as-made PdAgSn/PtBi HEA NPs show excellent electrocatalytic activity and durability for methanol oxidation reaction (MOR) and ethanol oxidation reaction (EOR). Especially, the specific (mass) activity of PdAgSn/PtBi HEA NPs for MOR is 4.7 mA/cm2 (2874 mA mg(Pd+Pt)-1), about 1.7 (5.9) and 1.5 (4.8) times higher than that of commercial Pd/C and Pt/C catalysts, respectively. Combined with high-entropy effect, Pt sites and Pd sites on the interface of the HEA act synergistically to facilitate the multi-step process towards EOR. This study offers a promising way to find a feasible route for scalable HEA manufacturing with promising applications.