This study employed a co-precipitation method to synthesize copper-modified hydroxyapatite (HA) powders, where Cu(2+) ions had entered the structure of HA and occupied Ca(1) sites in the columns parallel to the c-axis. Through a hydrothermal treatment, hollow HA/copper (Cu(2)O and/or Cu) microspheres with core-shell structures were prepared in solutions containing glucose, sodium carbonate and sodium citrate. When prolonging the reduction time, Cu(2+) ions dissolved from copper-modified HA were reduced by glucose initially to Cu(+) ions and then to Cu atoms, which would precipitate as copper on the surface of HA. The formation of microspheres with hollow structures was explained by the Kirkendall effect which states that diffusion behaviors of ions were different for HA and copper precipitations. Hybrid HA/copper powders might find their applications in gas sensors, catalysts, electrodes and so on.