Abstract: Objective: To explore the expression of claudin-3,4 in human esophageal squamous cell carcinoma and adjacent normal esophageal mucosa and its clinical significance.Methods: Immunohistochemistry SP method was used to detected the expressions of claudin-3,4 protein and clinicopathological characteristics in fifty-four cases of esophageal squamous cell carcinoma and twenty-six cases of adjacent normal esophageal tissue.Results: The positive expression rate (92.6%) of claudin-3 protein in esophageal squamous cell carcinoma was significantly higher than adjacent normal esophageal mucosa (15.4%) (P<0.01),the expression of claudin-3 protein was unrelated with sex,age,tumor size,histological grade,TNM stage,lymph node metastasis (P>0.05),but was related with distant metastasis,the positive rate in distant metastasis were lower than those without distant metastasis (P<0.05).The expression of claudin-4 protein was related with age and distant metastasis,the positive rate in distant metastasis and ≤ 60 years old were lower than those without distant metastasis (P<0.05) and patients>60 years (P<0.01).Conclusions: Claudin-3,4 plays a catalytic role in esophageal squamous cell carcinoma pathogenesis,but when there is distant metastasis,the expression is low or lack.