Abstract: Objective To investigate the expression of claudin-3 in colorectal carcinoma and its association with the occurrence, progression and prognosis of colorectal cancer. Methods Forty surgical specimens of colorectal carcinoma and 22 adjacent normal tissues resected between October, 2010 and January, 2013 at Nanfang Hospital were examined for claudin-3 expression using immunohistochemistry, which was analyzed in association with the clinicopathological parameters and the survival of the patients. Results Claudin-3 was expressed mainly on the cell membrane, and its positivity rate was significantly higher in cancer tissues than in normal tissues (92.50% vs 59.09%, P<0.05). In 13 cases claudin-3 expression was detected in both the cancer tissues and adjacent normal tissues with average expression scores of 4.538 and 3.269, respectively (P<0.05). In the cancer tissues, the strongly positive expression rate was significantly higher in poorly differentiated tissues (85.71%) than in well (21.43%) and moderately (36.48%) differentiated tissues (P<0.05), and was higher in cases with lymph node metastasis than in those without (61.11% vs 22.72%, P<0.05). The strongly positive expression rate of claudin-3 was not correlated with the patients’age, gender, tumor location or tumor size (P>0.05). Of the 33 cancer patients followed up, 14 had a postoperative survival time no longer than 3 years and 19 had longer survival time, and their average expression scores differed significantly (4.50 vs 3.526, P<0.05). Conclusion Claudin-3 is over-expressed in colorectal cancer tissues, and its high expression may promote the occurrence and progression of colorectal cancer. Claudin-3 may serve as a molecular biomarker for early diagnosis and prognostic evaluation.