AbstractProstate cancer causes a high frequency of bone metastases. The purpose of this study was to identify molecules that regulate prostate cancer bone metastasis as potential therapeutic and/or prognostic targets in prostate cancer, using integrative genome‐wide data. Based on the biological characterization of prostate cancer cell lines and integrated big data analysis of clinical samples, we identified CTHRC1 as a candidate gene that regulates prostate cancer bone metastasis. The knockdown of CTHRC1 suppressed cell migration and cell adhesion, but not cell proliferation, in vitro and in vivo. In a mouse tibia xenograft model, CTHRC1 knockdown markedly suppressed metastatic growth of prostate cancer cells in the bone microenvironment. CTHRC1 also promoted in vitro osteoclast differentiation. The analysis of 343 human prostate cancer biopsy samples showed that CTHRC1 expression was positively correlated with bone metastasis, indicating that CTHRC1 could be a useful predictive marker for bone metastasis. Our findings illustrate the clinical relevance of CTHRC1 and demonstrate that CTHRC1 plays an important role in prostate cancer bone metastasis. CTHRC1 may be useful for predicting prostate cancer bone metastasis and may lead to the development of new methods for the prevention and treatment of metastasis.