AIM: To study the relationship between the expression of human chorionic gonadotropin (HCG), CD44v6,CD44v4/5 and the infiltration, metastasis of esophageal squamous cell carcinoma. METHODS: By labeled streptavidin-biotin technique,the expressions of HCG, CD44v6, and CD44v4/5 in 42 patients with esophageal squamous cell carcinoma were examined.RESULTS: The positive rate of HCG expression in patients with lymph node metastasis was 85.71%(18/21), higher than that (57.14%, 12/21) in those without lymph node metastasis (P＜0.05). The positiverate of CD44v6 expression was 71.43% (15/21) in lymph node metastasis group, and 38.09% (8/21) in nonmetastasis group; there was a significant difference between the two groups (P＜0.05). The positive rateof CD44v4/5 expression was 76.19% (16/21) inlymph node metastasis group, and 42.86% (9/21) in non-metastasis group; there was also a significant difference between them (P＜0.05). From grade I to grade Ⅲ in differentiation, the positive rate of HCG expression was 84.62% (11/13), 70.59% (12/17) and 58.33% (7/12), respectively; there was no significant difference among them (P＞0.05). The positive rate of CD44v6 expression in grades Ⅰ -Ⅲ of cancer tissues was 76.92% (10/13), 52.94% (9/17), and 33.33%(4/12) respectively; there was no significant difference among them. The positive rate of CD44v4/5 expression in grades Ⅰ-Ⅲ of cancer tissues was 69.23% (9/13),64.71% (11/17), and 41.67% (5/12) respectively; there was no significant difference among the three groups. There was no correlation between the positive rates ofHCG and CD44v6, CD44v4/5 expression. Cancer cells in carcinomatous emboli and those infiltrating into vascular wall strongly expressed HCG, CD44v6, and CD44v4/5. CONCLUSION: Expression of HCG, CD44v6, and CD44v4/5 in esophageal squamous cell carcinoma is related to its infiltration and metastasis. HCG, CD44v6, and CD44v4/5 have different effects on the infiltration and metastasis of esophageal squamous cell carcinoma.