Due to strain and ligand effects, the simultaneous presence of concave and convex surfaces and their highly-defective nanostructure (atomic vacancies, grain boundaries), hollow Pt-rich/C electrocatalysts have proven to enhance remarkably the oxygen reduction reaction (ORR) kinetics. However, a technologically-relevant proton-exchange membrane fuel cell (PEMFC) cathode catalyst should be able to maintain its initial catalytic activity on the long-term. This is hardly feasible on nanocatalysts based on platinum alloyed with transition metals (PtM alloys, M being a transition metal) or M-rich core@Pt-rich shell nanoparticles due to the dissolution of the transition metal in the harsh operating conditions of a PEMFC cathode but the question remains open for nanocatalysts in which catalytic activity is not solely due to alloying effects. Herein, the ORR activity of solid or hollow PtNi/C nanoparticles with identical chemical composition but different fine nanostructure was evaluated before and after accelerated stress tests (ASTs) under simulated PEMFC operating conditions (5,000 potential cycles between 0.6 and 1.0 V vs. RHE at T = 80°C). Independently on the nanostructure, the combined physical, chemical and electrochemical results show that the losses in ORR activity are related to weakening of strain and ligand effects associated with the dissolution of Ni atoms. However, the catalytic advantage of hollow over solid PtNi/C nanoparticles was maintained during the ASTs. Hence, implementing structural disorder in PEMFC cathode electrocatalysts represents a new direction to look at to improve sustainably the ORR kinetics.