Hydroxyapatite (HA) is widely used in filling of bone defects and coating on metal parts of prosthetic implants due to its excellent biocompatibility, bioactivity, and bone-bonding properties. It has been demonstrated that micro-sized HA particles cause inflammatory reaction, especially for the needle shaped particles. However, little effort has been concentrated on the cell responses of the spherical HA nanoparticles. The aim of the present work is to chemically and physically characterize the synthesized HA nanoparticles and to investigate the in vitro cell responses. X-ray diffraction, electron microscopy, nitrogen adsorption, and Fourier transform infrared spectroscopy revealed that the particles consisted of nearly spherical crystallites of carbonate-substituted HA with size of 20-40 nm and specific surface area of 75 m(2)/g. L929 cell proliferation experiments demonstrate that the spherical HA nanoparticles is more biocompatible than commercially available HA. On the other hand, U2-OS cell test results show that the inhibition rate of the spherical HA nanoparticles increases with time and concentration. The half effective inhibitory concentration (IC50) of the nanoparticles was determined to be 50.8 mug/mL at 72 h. All these data indicated that the synthesized spherical nanocrystalline HA particles can function as an effective biomaterial for bone tumorectomy repair, while having little adverse effect.