Objective:To investigate relationship between DNA polymerase iota (Polι) and lymph node metastasis of human esophageal squamous cell carcinoma. Methods:Polι expression in esophageal squamous cell carcinoma tissues was detected by Real-time PCR. Mann-Whitney U test was performed to analyze the relationship between Polι and lymph node metastasis. Polι and Nm23 expression in esophageal squamous cell carcinoma tissues was detected by immumohistochemical staining. Spearman correlation analysis was performed to analyze the relationship between Polι and Nm23. The Polι expression vector was transfected into esophageal cancer cells TE-1 and ECA-109 to up-regulate Polι expression. Polι and Nm23 mRNA expression was detected by Realtime-PCR. Transwell chamber assay was performed to analyze cell invasional ability. Results:In clinical tissue samples,Polι expression was positively correlated with the lymph node metastasis of human esophageal squamous cell carcinoma (P < 0.01),and negatively correlated with Nm23 in protein level (R=-0.481,P < 0.05). In vitro study,overexpression of Polι enhanced cell invasion (P < 0.05) and significantly inhibited Nm23 mRNA expression in TE-1 and ECA-109 cells (P < 0.001). Conclusion:Polι is closely related with the invasion and metastasis of esophageal squamous cell carcinoma,the possible mechanism of the regulation is through down regulating the expression of Nm23.