Rationale:　Bone　is　the　most　frequent　site　for　breast　cancer　metastasis,　which　accounts　for　the　leading　cause　of　death　in　advanced　breast　cancer　patients.　Serious　skeletal-related　events　(SREs)　caused　by　bone　metastasis　have　a　decisive　impact　on　the　life　expectancy　of　breast　cancer　patients,　making　breast　cancer　almost　incurable.　Metastatic　breast　cancer　cell　induced　pathological　osteoclastogenesis　is　a　key　driver　of　bone　metastasis　and　osteolytic　bone　lesions.　We　previously　reported　that　gold　clusters　can　prevent　inflammation　induced　osteoclastogenesis　and　osteolysis　in　vivo.　In　this　study,　we　investigated　the　effects　of　a　BSA-coated　gold　cluster　on　metastatic　breast　cancer-induced　osteoclastogenesis　in　vitro　and　tumor-induced　osteolysis　in　vivo,　and　elucidated　its　possible　mechanism.　Methods:　Breast　cancer　cell　line　MDA-MB-231　was　used　to　evaluate　the　regulatory　effects　of　gold　clusters　on　breast　cancer　metastasis　and　tumor　induced　osteoclastogenesis　in　vitro.　Cell　counting　kit-8,　transwell,　wound-healing　and　colony　formation　assays　were　performed　to　evaluate　the　effect　of　gold　clusters　on　proliferation　and　metastasis　of　MDA-MB-231　cells.　Tartrate-resistant　acid　phosphatase　(TRAP)　staining　and　filamentous-actin　rings　analysis　were　used　to　detect　the　regulatory　effects　of　gold　clusters　on　MDA-MB-231　cell-conditioned　medium　(MDA-MB-231　CM)　triggered　and　receptor　activator　of　nuclear　factor-kappa　B　ligand　(RANKL)-induced　osteoclastogenesis　in　mouse　bone　marrow-derived　mononuclear　cells　(BMMs).　A　mouse　model　of　breast　cancer　bone　metastasis　was　used　to　evaluate　the　in　vivo　activity　of　the　gold　cluster　on　the　tumor　induced　osteolysis.　Results:　The　gold　clusters　suppressed　the　migration,　invasion　and　colony　formation　of　MDA-MB-231　cells　in　a　dose-dependent　manner　in　vitro.　The　gold　clusters　strongly　inhibited　both　MDA-MB-231　CM　triggered　and　RANKL-induced　osteoclast　formation　from　BMMs　in　vitro.　Cell　studies　indicated　that　the　gold　clusters　suppressed　the　expression　of　osteolysis-related　factors　in　MDA-MB-231　cells　and　inhibited　the　subsequent　activation　of　NF-kappa　B　pathway　in　BMMs.　Treatment　with　the　clusters　at　a　dose　of　10　mg　Au/kg.bw　significantly　reduces　the　breast　cancer　cell　induced　osteolysis　in　vivo.　Conclusion:　Therefore,　the　gold　clusters　may　offer　new　therapeutic　agents　for　preventing　breast　cancer　bone　metastasis　and　secondary　osteolysis　to　improve　patient　outcomes.