The effects of hydroxyapatite nanoparticles (HA-NPs) on two kinds of cells, human MG63 cells and the normal osteoblasts were investigated. According to the MTT assay and fluorescent staining assay, it was proved that HA-NPs could inhibit the growth of MG63 cells but slightly support proliferation of the osteoblasts. Meanwhile, transmission electron microscopy (TEM) was employed to observe the ultrastructural alterations of both cells. The TEM results showed that HA-NPs had entered the two kinds of cells. Typical apoptosis was observed in the MG63 cells, especially in the group of 250 μg/mL with 5 days culture. While no apoptosis could be found in the normal osteoblasts at any concentration group of HA-NPs. Our results suggested that the HA-NPs had selective effects to different kinds of cells: supporting proliferation to the normal bone cells while causing apoptosis to the osteosarcoma cells.