Objective To explore the effect of miR-126 on proliferation and apoptosis in colon cancer cells via targeting regulation of SOX2 expression. Methods miR-126 mimics and miR-126 NC were transfected into SW480 cells by liposome LipofectamineTM2000. The expression of miR-126 was detected by RT-PCR. Cell viability was determined by MTT staining. Cell apoptosis and cell cycle were detected by flow cytometry. The expression of SOX2 protein and mRNA was measured by western blot and RT-PCR. Luciferase reporter analysis was performed. Results Compared with miR-126 NC, the expression of miR-126 was upregulated ( P < 0.01), cell viability was reduced ( P < 0.01), early cell apoptosis rate and late apoptosis rate were increased ( P < 0.01), cell cycle was arrested at G1 phase ( P < 0.01), meanwhile, miR-126 mimics targeted downregulation of the expression of SOX2 protein and mRNA ( P < 0.01). Conclusions miR-126 mimics can inhibit SW480 cell proliferation and induce cell apoptosis by targeting downregulation of expression of SOX2.