AIM: To characterize p62 expression and define the relationship between p62 expression and cell proliferation in primary carcinomas of the digestive system.METHODS: p62 expression was characterized in surgically resected tumor specimens from 60 patients with primary carcinomas of the digestive tract (including 22 esophageal carcinomas, 17 gastric carcinomas, and 21 colorectal carcinomas) and 40 patients with hepatocellular carcinoma (HCC) by immunohistochemistry (IHC). The cell proliferation was determined by IHC of Ki-67 in 40 patients with HCC.RESULTS: Twenty-two cases of esophageal carcinomawere histopathologically diagnosed as squamous cell carcinoma. We combined the gastric and colorectal carcinomas based on the equivalent histology. The 38tumors in the combined groups, consisted of 17 welldifferentiated, eight moderately differentiated, nine poorly differentiated carcinomas, and four mucinous adenocarcinomas. According to the criteria of Edmondson and Steiner, 40 patients with HCC were graded (2 grade Ⅰ, 17 grade Ⅱ and 21 grade Ⅲ). p62 expression in primary carcinomas of the gastrointestinal tract (60/60,100%)was higher than that (27/40, 67.5%) of HCC (P＜0.01,χ2 = 19.63). High expression levels of p62 were positively correlated with histological grades in gastric and colorectal carcinomas (P＜0.0001) and inversely associated with those in HCC (P = 0.0322). No significant correlations were observed for esophageal carcinomas (P = 0.8246).p62 expression was also detected in the cytoplasm of morphologically normal columnar epithelial cells adjacent to the cancer foci of gastric and colorectal carcinomas.In 40 HCC specimens, the mean Ki-67 labeling index (LI)was (19.6±16.0)%. It was (28.3±18.73)% in 12 cases with high p62 expression (+++), (7.53±14.83)% in 13 cases without p62 expression(-). Patients with a high p62expression showed a significantly higher level of Ki-67 staining than those without p62 expression (P＜0.05, t = 2.069).CONCLUSION: p62 expression is common in carcinomas of the digestive system and higher in carcinomas of the gastrointestinal tract than in primary HCC. p62 is a cellular differentiation-related protein. Cancer cells with a high p62 expression exhibited highgrowth fractions in HCC.