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Objective. To investigate the roles and possible mechanisms of SIRT2 and KLF4 in the development and progression of myeloma. Methods. Rt-PCR was used to detect SIRT2 in myeloma samples from patients and myeloma cells, the expression level of KLF4 in myeloma cells, and the effect of downregulation of SIRT2 expression on KLF4 expression level. MTT assay and wound-healing assay were used to observe the proliferation and migration of U266cells transient transfected with Sirt2 inhibitors. Results. SIRT2 is highly expressed in myeloma, but KLF4 was down. Downregulation of SIRT2 expression stimulated the expression level of KLF4. Reduced SIRT2 activity results in the release of KLF4 expression, which inhibits the proliferation and migration of myeloma cells. Conclusion. SIRT2-KLF4 combination plays an important role in the occurrence and development of myeloma. [ABSTRACT FROM AUTHOR]