In this study, we describe for the first time that Bazedoxifene with the novel function as GP130 inhibitor inhibits STAT3 phosphorylation, induces apoptosis, reduces cell viability in rhabdomyosarcoma cells, blocks angiogenesis and invasion, and suppresses the tumor growth in human rhabdomyosarcoma xenograft, suggesting that Bazedoxifene may serve as a novel therapeutic drug for rhabdomyosarcoma treatment by targeting IL-6/GP130 signaling pathway. The gene discussed is STAT3; the disease is rhabdomyosarcoma.