This study aimed to explore the effect of SIRT6 gene expression on the proliferation of colorectal cancer cells to improve our understanding of the pathogenesis of colorectal cancer. The colorectal cancer cell lines LOVO, SW480, SW620, LS-174T, HCT-8, and HCT-116 were employed to screen the expression of the SIRT6 gene using real-time Quantitative Polymerase Chain Reaction (Q-PCR). The expression of SIRT6 was also determined in polyp tissues, colorectal cancer tissues, and the tissues adjacent to the carcinomas using Q-PCR. After that, the SIRT6 gene was transfected into the colorectal cancer cell lines SW620 and LOVO to investigate its effects on cell proliferation, the cell cycle, and apoptosis. The expression of SIRT6 in polyp tissues was significantly higher than its expression in colorectal cancer cell lines and colorectal cancer tissue (P<0.05). However, its expression in tumors and nearby tissues showed no significant differences compared to colorectal cancer cell lines (P>0.05). There was also no significant difference between the expression of SIRT6 in the adjacent tissues and the expression in the polyp tissues (P>0.05). Following the transfection of the SIRT6 gene, the growth of both SW620 and LOVO cells was inhibited. This was due to changes in the cell cycle and significant increases in apoptosis in SW620 cells. However, no obvious apoptosis was observed in LOVO cells. Thus, the SIRT6 gene plays a role as a suppressor of the pathogenesis of colorectal cancer.