Objective: To investigate the expression of the endoplasmic reticulum stress (ERS)-related protein CHOP/GADD153 in colon cancer and its relations with clinicopathologic characteristics. Methods: The specimens of colon cancer tissue and normal adjacent colonic tissue (>5 cm distance from cancer tissue) were taken from 82 colon cancer patients and casted into paraffin blocks for tissue microarray construction. The CHOP/GADD153 protein expression was detected by immunohistochemical staining and Western blot analysis respectively, and the relations of its expression with clinicopathologic characteristics of the patients were analyzed. Results: Both results of immunohistochemical and Western blot analysis showed that the expression level of CHOP/GADD153 protein in the colon cancer tissue was significantly higher than that in normal adjacent colonic tissue (P<0.05). The analysis of relationship between CHOP/GADD153 protein expression and clinicopathologic profiles indicated that the expression level of CHOP/GADD153 protein in colon cancer tissue was increased with the decrease of the degree of tumor differentiation (P<0.05), but was irrelevant to age, sex, tumor size, tumor infiltration depth and lymph node metastasis (all P>0.05). Conclusion: CHOP/GADD153 protein expression is increased in colon cancer tissue, and is closely related to degree of differentiation of colon cancer, which suggests that ERS may probably participate in the regulation of tumor differentiation.