Hydroxyapatite (HA) has been widely applied in bone repair because of its superior biocompatibility. Recently, a proliferation-suppressive effect of HA nanoparticles (n-HA) against various cancer cells was reported. This study was aimed at assessing the translational value of n-HA both as a bone-regenerating material and as an antitumor agent. Inhibition of tumor growth, prevention of metastasis, and enhancement of the survival rate of tumor-bearing rabbits treated with n-HA were demonstrated. Activated mitochondrial-dependent apoptosis in vivo was confirmed, and we observed that a stimulated immune response was involved in the n-HA-induced antitumor effect. A porous titanium scaffold loaded with n-HA was fabricated and implanted into a critical-sized segmental bone defect in a rabbit tumor model. The n-HA-releasing scaffold not only showed a prominent effect in suppressing tumor growth and osteolytic lesion but also promoted bone regeneration. These findings provide a rationale for using n-HA in tumor-associated bone segmental defects.