Calcium carbonate/carboxymethyl chitosan (CaCO3/CMC) hybrid microspheres and nanospheres were prepared by the precipitation of calcium carbonate in an aqueous solution containing CMC. Through adjusting the preparation conditions, the size of CaCO3/CMC hybrid particles could be easily controlled at micro- to nanometer ranges with relatively narrow size distributions. The obtained microspheres and nanospheres were characterized by scanning electron microscopy, Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, thermogravimetric analysis, and differential scanning calorimetry. The size and size distribution were measured by a particle size analyzer. Doxorubicin hydrochloride (DOX·HCl), a water-soluble anticancer drug, was loaded in the hybrid microspheres and nanospheres with a high encapsulation efficiency. The in vitro drug release showed that the release of DOX·HCl from the microspheres and nanospheres could be effectively sustained.