Objective To explore the role and mechanism of RANKL in bone metastasis of breast cancer. Methods MDA-MB-231 breast cancer cells were cultured in vitro and divided into control group and RANKL group. The RANKL group was added with a final concentration of 200ng/ml RANKL. Add the same volume of double distilled water to the control group. Compare the migration ability of two groups using Transwell. Single cell calcium imaging was used to detect the effect of RANKL on the calcium response of BT549 and MCF-7 breast cancer cells. Western blot and PCR were used to detect the effect of RANKL on EMT process of breast cancer cells. The luciferase reporter gene system explores the possible molecular mechanism of RANKL mediated EMT in breast cancer. Results Compared with the control group, the RANKL group showed stronger migration and invasion ability (P<0.05). RANKL stimulation leaded to calcium oscillations in breast cancer cells and increased the calcium response rate of breast cancer cells. RANKL promoted the EMT of breast cancer cells. In the presence of RANKL, Ca2+ promoted the EMT process of breast cancer cells in a dose-dependent manner, specifically, E-cadherin decreases and N-cadherin increased. The luciferase reporter gene system shows that RANKL significantly activates NF- κ B (Nuclear Factor Kappa B) signaling pathway.Conclusion RANKL induced calcium signaling via NF-κB pathway enhances the EMT process of breast cancer cells and promotes bone metastasis of breast cancer.