Background and purpose: It was reported that nuclear factor of activated T cells (NFAT)　is closely related with carcinomas. Esophageal squamous cell carcinoma (ESCC) is one of the most common carcinomas in China. The present study investigated the expression and clinical significance of NFAT isoforms in ESCC. Methods: The expression of NFAT isoforms and the differences in different pathological levels of ESCC were detected in 104 specimens of human ESCC tissues and normal esophageal tissues by immunohistochemistry. Results: This study found that the positive rates of NFAT1 (53.8%)

NFAT2 (10.6%)

NFAT3 (26.9%)

NFAT4 (45.2%) expression were significantly higher in tumor tissues than in adjacent normal esophageal tissues (P0.001)

respectively. The positive rate of NFAT1 expression was significantly higher in drinkers (62.3%) than nondrinkers (37.1%

P=0.01)

and also higher in patients with lymph node metastasis (68.4% vs 5.5%

P=0.002) and with late stage (58.7% vs 36.2%

P=0.02). Multivariate analysis showed that NFAT1 expression was correlated with lymph node metastasis. The positive rate of NFAT3 was significantly higher in patients with lymph node metastasis (39.4%) than in those without lymph node metastasis (19.7%

P=0.03). Conclusion: These results suggest that the overexpression of NFAT1 and NFAT3 is associated with lymph node metastasis in ESCC.