Objective: To investigate the influence of octreotide on apoptosis and cell cycle in human colon cancer cells and the mechanism. Methods: Human colon cancer SW480 cells were exposed to octreotide or GSK-3β inhibitor LiCl alone or in combination; the apoptosis and cell cycle in SW480 were analyzed by flow cytometry, and the apoptosis was also verified by DNA agarose gel electrophoresis. In addition, the expressions of GSK-3β, p-GSK3β (Tyr216) and p-GSK3β (Ser9) in SW480 cells were determined by Western blot analysis. Results: Compared with the blank control group of untreated SW480 cells, in SW480 cells after octreotide treatment, the apoptosis and ratio of G0/G1 phase cells were significantly increased, typical DNA ladders were present in the agarose gel electrophoresis, and the total GSK-3β protein and p-GSK3β (Tyr216) protein expressions were significantly increased, while the p-GSK3β (Ser9) protein expression was significantly decreased (all P<0.05); LiCl treatment alone exerted no influence on apoptosis and cell cycle in SW480 cells (both P>0.05), but it significantly weakened the apoptosis-inducing and cell cycle arrest effect of octreotide in SW480 cells in combination with octreotide (both P<0.05). Conclusion: Octreotide can effectively induce apoptosis and cell cycle arrest in SW480 cells, which may be related to its increasing GSK-3β protein expression and regulating phosphorylation level of GSK-3β.