Objective: To investigate the expression of vesicle-associated membrane protein 8 (VAMP8) in colon cancer tissue and its clinical significance. Methods: The specimens of colon cancer along with normal adjacent tissue from 42 patients were collected, in which the positive expression rate of VAMP8 protein was detected by immunohistochemical staining, and then the relations of VAMP8 expression with clinicopathologic characteristics of the patients were analyzed. Further, 12 pairs of the specimens were selected, and then the VAMP8 mRNA and protein expression levels were determined by qRT-PCR and Western blot, respectively. Results: Results of qRT-PCR and Western blot analysis showed that the VAMP8 mRNA and protein expression levels in colon cancer tissue were significantly higher than those in their matched adjacent tissue in 9 pairs of specimens (both P<0.05). Results of immunohistochemical staining demonstrated that the positive expression rate of VAMP8 protein in colon cancer tissues was significantly higher than that in adjacent non-tumorous tissues (73.8% vs. 42.9%; χ2=8.28, P<0.01), and the VAMP8 expression was significant associated with histopathological grade, Dukes’ stage and lymph node metastasis (all P<0.05). Conclusion: VAMP8 expression is increased in colon cancer tissue, which suggests that VAMP8 may promote the progression and metastasis of colon cancer through regulating the autophagy-lysosome pathway.