Objective To investigate the inhibitory effect and possible molecular mechanism of Fuzheng Guben method on bone destruction after breast cancer bone metastasis. Methods Animal model of breast cancer bone metastasis was established by tibia injection of breast cancer cells, then treatment group mouse were given Fuzheng Guben formulas. The growth, bone destruction and osteoclast activity of breast cancer in bone environment were detected by IVIS, X-ray and TRAP staining respectively. The expression of serum cytokines, such as TNF-α, IL-1β, IL-6, IL-17, PTHrP, RANKL, OPG, TGF-β, IGF and PDGF were used ELISA analysis. Results IVIS showed that growth of breast cancer in bone environment was slow down after treated with Fuzheng Guben formulas, X-ray and TRAP staining showed that bone destruction and osteoclast activity was reduce in Fuzheng Guben group, ELISA showed that Fuzheng Guben reduced the expression of TNF-α, IL-1β, IL-6, IL-17, PTHrP, RANKL, TGF-β, IGF、PDGF and improved the expression of OPG in mouse serum. Conclusion Fuzheng Guben method inhibited proliferation of breast cancer cells in bone environment and reduced the bone destruction by regulating the expression of various cytokines.