Objective: The aim of our study was to investigate the effect of bertezomib in combination with arsenic trioxide (As2O3) on the proliferation and apoptosis in the human multiple myeloma cell line KM3. Methods: KM3 cells were cultured with different concentrations of bortezomib, AS2O3 alone or in combination for different times. Cell proliferation was analyzed by MTT assay, and the IC50 was calculated. Cell morphology was observed under the light microscope (using Wright-Giemsa stain) and electric microscope. Agarose gel electrophoresis was used to evaluate DNA content. Flow cytometry was used to examine Annexin V-FITC/PI stain and mitochondrial transmembrane electric potential (△ψUm). Results: Bortezomib and As2O3 alone both inhibited KM3 cell proliferation in a time and dose dependent manner, with the IC50 were 0.27, 3.10 μmol/L,respectively; the inhibiting rate on KM3 calls of bortezomib plus As2O3 was significantly higher than bortezomib alone (18.22 ±1.04)% vs. (13.18±1.29)%, P < 0.05; A series of typical morphological features of apoptosis and a typical DNA ladder were observed in KM3 cell treated with 0.25 μmol/L bortezomib for 48 h, which showed increased Annexin V positivity and decreased △ψm. The apoptosis rate induced by bortezomib plus As2O3 was also significantly than that of induced by bortezo-mib alone. Conclusion: Bortezomib could inhibit the proliferation while induce apoptosis of KM3 cells which may be through decreased △ψm. Bortezomib had enhanced inhibitory effect with As2O3 on the growth of KM3 cell (P < 0.05). As2O3 enhancesthe apoptosis effects of bortezomib on KM3 cell.