A novel strategy for the synthesis of mesoporous metal oxide polyhedra with empty nanovoids by introducing nanoscale Kirkendall diffusion into a spray pyrolysis process is suggested. In this study, NiSe polyhedra with high index facets synthesized by one-pot spray pyrolysis were transformed into mesoporous NiO polyhedra with empty nanovoids by a facile oxidation process at 500?°C through nanoscale Kirkendall diffusion. Details of the formation mechanism of these uniquely structured NiO polyhedra were also studied. In the initial oxidation step, a thin NiO layer was formed on the surface of the NiSe polyhedra. The fast diffusion of Ni cations out through the NiO layer and the melting of the remaining metalloid Se formed a porous Se layer. The formation of a mesoporous NiO layer then enabled the penetration of oxygen gas by gas phase diffusion. The diffusion of metalloid Se into the mesopores of NiO and its reaction with oxygen gas formed SeO₂ nanocrystals which then evaporated into the gas phase. The step-by-step oxidation of the NiSe crystals therefore resulted in mesoporous NiO polyhedra with empty nanovoids. When used as an anode material in a lithium ion battery, mesoporous NiO polyhedra with empty nanovoids showed superior cycling and rate performance compared to anodes fabricated from dense-structured NiSe polyhedra and commercial NiO nanopowders. The mesoporous NiO polyhedra showed a high discharge capacity of 1072?mA?h?g^?1 after 200 cycles at a current density of 1.0?A?g^?1 and they showed a high reversible capacity of 453?mA?h?g^?1, even at a high current density of 15.0?A?g^?1.