Objective:To investigate the effect of bortezomib on multiple myeloma stem cells. Methods:In this study,we cultured human multiple myeloma cell lines KMS-11 and the OCI-MY5 in vitro and set the control group and experimental group of bortezomib treatment. To analyze the proportion of side population cells by using flow cytometry and the mechanism of cancer stem cells efflux Hoechst 33342. Results:After treatment,we found that side population cells were significantly increased. Conclusion:The results indicate that the target of bortezomib is non-side population cells and providing an objective basis for the sequential therapy of bortezomib.