The ability to precisely control the nanoscale phase structure of bimetallic catalysts is required to achieve a synergistic effect between two metal for oxygen reduction reaction (ORR). In this work, we synthesized Pt-Ag bimetallic nanoparticles (NPs) with Ag@Pt core-shell, highly alloyed solid and hollow nanostructures respectively, via a galvanic replacement reaction by modifying H 2 PtCl 6 concentration in an aqueous solution containing homemade Ag NPs as the sacrificial templates. The nanophase and corresponding electronic structures of the synthesized Pt-Ag NPs were characterized by transmission electron microscopy, X-ray diffraction, and X-ray photoelectron spectroscopy. The formation of these Pt-Ag NPs with different 2 nanophase structures is closely ascribed to a defect-induced Kirkendall effect that involves the accelerated interdiffusion of Ag and Pt atoms, triggered by the high density of defects along the Ag NP surface generated by the galvanic replacement reaction. The nanophase structure-dependent electrocatalytic activity of three Pt-Ag bimetallic NPs was determined in 0.5 M H 2 SO 4 solution by using a rotating disk electrode (RDE). The results showed that the core-shell and hollow alloy NPs exhibit the excellent ORR activity in an acidic solution, which is remarkably higher than that of the commercial Pt/C (E-TEK). The physical origin of the enhancement in the ORR activity can be explained by a mutual ligand effect, raised by the substantial electronic transfer between Pt and Ag at the atomic level, which results from the downshift of the d-band center for Pt and the increased number of the unpaired electrons for Ag in these bimetallic catalysts. Thus two factors achieve a synergistic effect that dominates the remarkably improved electrocatalytic activity for the ORR.