〔Abstract〕 Objective To investigate the effect of sinomenine on proliferation and migration of multiple myeloma(MM) cells by regulating STAT3 and NF-κB signaling pathway. Methods The cultured U266 cells were treated with different concentrations of sinomenine(0,0.5,1,2 mmol/L).The control group was added DMSO with 0.5% concentration.CCK-8 assay was used to detect the proliferation of U266 cells.Flow cytometry was used to detect the apoptosis of U266 cells.Western blot assay was used to detect the expression levels of apoptosis-related proteins, STAT3 and NF-κB signaling pathway proteins in the each group. Results Compared with CON group, the apoptosis of U266 cells increased after Sinomenine treatment, the proliferation was inhibited; B lymphoma-2(Bcl-2) myeloid and cell leukemia-1(Mcl-1) expression level decreased; activated Caspase-3(cleaved Caspase-3) and PARP(Cleaved Caspase-3) expression levels increased; the activity of STAT3 and NF-κB signaling pathway decreased. Conclusion Sinomenine can down-regulate the activity of STAT3 and NF-κB signaling pathway, promote the apoptosis of U266 cells and inhibit the proliferation of U266 cells.