〔Abstract〕 Objective To investigate the effect of SIRT6 on the proliferation and migration of renal cancer cell lines ACHN and 786-O. Methods Immunohistochemistry was used to detect the expression of SIRT6 in renal cell carcinoma and adjacent tissues; Western blot was used to detect the expression levels of kidney cancer cell line SIRT6 and related downstream signaling pathway molecules; SIRT6-siRNA transfection and SIRT6 specific inhibitor OSS_128167 were used to treat ACHN cells, Scratch test and Tetramethylazazole blue test were usedto observe the proliferation and migration ability of treated ACHN cells, and Western blot was used to detect changes in downstream related signal pathways. Results The results of immunohistochemistry and Western blot showed that the expression of SIRT6 in renal cancer tissues was significantly higher than that in adjacent tissues. Compared with normal renal tubular epithelial cells HK-2, the expression of SIRT6 in renal cancer cell line ACHN significantly increased. After transfection of ACHN with SIRT6-siRNA, the expression of SIRT6 was significantly reduced. Scratch test and MTT showed that the proliferation and migration ability of ACHN cells was reduced. After OSS_128167 treatment of renal cancer cell lines, the deacetylation activity of SIRT6 decreased, and the cell proliferation ability decreased. Conclusion The SIRT6 deacetylase can inhibit the proliferation and migration of renal cancer cells by down-regulating the PI3 K-AKT pathway, and may become a potential new target for drug therapy.