The electrical performance of a Proton Exchange Membrane Fuel Cell (PEMFC) is limited by the sluggish oxygen reduction reaction (ORR) kinetics. Thereby, the high platinum content needed at the cathodic catalytic layer to compensate these poor kinetics creates a major cost barrier for massive commercialization of PEMFC systems. Due to the strain and ligand effects, alloyed PtM/C or M-rich core@Pt-rich shell catalysts (where M is an early or late transition metal) have demonstrated tremendous ORR catalytic improvements compared to pure Pt/C. In this study, we synthetized and characterized nanometre-sized PtNi/C electrocatalysts with low Ni content (~15 at. %) but different nanostructures and different grain boundary densities: solid, hollow or “sea sponge” PtNi/C nanoalloys, Ni@Pt/C core@shell nanoparticles and solid Pt/C nanoparticles. These nanostructures were characterized by transmission and scanning-transmission electron microscopy, X-ray energy dispersive spectroscopy, Synchrotron wide-angle X-ray scattering, atomic absorption spectroscopy and electrochemical techniques. Their electrocatalytic activities for the ORR were determined, and structure-activity relationships established. The results showed that (i) the compression of the Pt lattice by 15 at. % Ni provides mild ORR activity enhancement compared to pure Pt/C, (ii) polycrystalline porous hollow nanoparticle feature dramatically enhanced ORR catalytic activity due to their highly defective nanostructure, (iii) the enhancement in ORR catalytic activity can be endorsed to the presence of grain boundaries as show two independent parameters: the microstrain determined from WAXS, and the average CO_ads electrooxidation potential determined from CO_ads stripping measurements. More results on methanol and ethanol electrooxidation suggest that structural defects produce a wide range of catalytic sites, resulting in versatile enhanced electrocatalytic performance.