 The synthesis of hollow CuO nanopowders by a salt-assisted spray drying process applying nanoscale Kirkendall diffusion is introduced. The electrochemical properties of the hollow CuO nanopowders for lithium-ion storage are also investigated. The first step of post-treatment of the spray-dried powders under a reducing atmosphere forms spherical and hollow NaCl powders embedded with Cu nanocrystals. Further post-treatment of the Cu–NaCl composite powders under an air atmosphere forms the spherical and hollow NaCl powders embedded with the hollow CuO nanopowders. Oxidation of the Cu nanocrystals under an air atmosphere produces hollow CuO nanopowders by nanoscale Kirkendall diffusion. The spherical and hollow CuO–NaCl composite powder transforms into ultrafine hollow CuO nanopowders by complete washing with distilled water to remove NaCl. The initial discharge and charge capacities of the hollow CuO nanopowders for lithium-ion storage at a current density of 1 A g−1 are 1077 and 781 mA h g−1, respectively. The reversible discharge capacity of the hollow CuO nanopowders for the 700th cycle is 803 mA h g−1.