The slow kinetics at the cathode of oxygen reduction reaction (ORR) seriously limits the efficiencies of fuel cells and metal-air batteries. Pt, the state-of-the-art ORR electrocatalyst, suffers from high cost, low earth abundance, and poor stability. Here a self-templated strategy based on metal-organic frameworks (MOFs) is proposed for the fabrication of hollow nitrogen-doped carbon spheres that are embedded with cobalt nanoparticles (Co/HNC). The Co/HNC manifests better ORR activities, methanol tolerance, and stability than commercial Pt/C. The high ORR performance of Co/NHC can be attributed to the hollow structure which provides enlarged electrochemically active surface area, the formation of more Co-N species, and the introduction of defects. This work highlights the significance of rational engineering of MOFs for enhanced ORR activity and stability and offers new routes to the design and synthesis of high-performance electrocatalysts.