The purpose of this study was to identify the role of interferon regulatory factor 7 (IRF7) in the bone metastasis of prostate cancer. Herein we demonstrated the lower expression of IRF7 in bone metastases of prostate cancer. Overexpression of IRF7 in prostate cancer cells had a marked effect on inhibiting bone metastases but not on tumor growth in xenograft nude mice. While in vitro, upregulation of IRF7 had little effect on the malignant phenotype of prostate cancer cells including proliferation, apoptosis, migration, and invasion. However, prostate cancer cells overexpressing IRF7 significantly enhanced the activity of NK cells, which resulted in the cytolysis of prostate cancer target cells. The underlying mechanism may be relevant to the increasing expression of IFN-β induced by IRF7, as the downregulation of which could inversely inhibit the activity of NK cells. In conclusion, our findings indicate that IRF7 plays a role in reducing bone metastasis of prostate cancer by IFN-β-mediated NK activity.