Fe2O3 nanoparticles is confined in the mesoporous shell of N-doped carbon microsphere for oxygen reduction reaction (ORR). A series of hollow catalysts together with corresponding control samples have been constructed, characterized and evaluated. The structure, composition and state of the as-prepared catalysts were characterized by Scanning electron microscope, Transmission electron microscope, X-Ray diffraction, X-Ray photoelectron spectroscopy, Raman and nitrogen adsorption-desorption. The electrochemical activity and selectivity of Fe2O3-based catalyst toward the 4e pathway has been greatly improved (E-onset of -50 mV, E-1/2 of -150 mV and average electron transfer number of 3.87). The current density is 18.5% higher than that of commercial 20 wt% Pt/C. Density functional theory calculations reveal that the confinement of Fe2O3 nanoparticles in the interlayer of N-doped graphite can significantly promote the activity of N-doped graphitic surface in alkaline media for ORR, due to facilitated O-2 adsorption and reduced energy of OOH formation which is the rate-determining step of ORR. Such a confinement strategy provides a general and effective route to push the limit of transition metal oxides to a higher level for ORR and realize the controllable construction of highly active non-noble-metal catalysts with well-defined mechanism understanding. (C) 2019 Elsevier Ltd. All rights reserved.