Objective To detect the expression of RAD51 and XRCC4 proteins in esophageal squamous cell line TE-1,normal esophageal epithelial cell line HEEp and esophageal squamous cell carcinoma with lymph node metastasis, and discuss the effects of RAD51 and XRCC4 on the occurrence, development and prognosis of esophageal squamous cell carcinoma. Methods The expression of RAD51 and XRCC4 proteins in TE-1 cells of esophageal squamous cell lines and HEEp of normal esophageal epithelial cells were detected by immunocytochemistry. Immunohistochemistry was used to detect the expression of RAD51 and XRCC4 proteins in 62 cases of esophageal squamous cell carcinoma with lymph node metastasis. Kaplan-meier was used to analyze the PFS of patients with positive and negative expression of RAD51 and XRCC4 protein. Results The immunocytochemical method showed that RAD51 and XRCC4 proteins were positively expressed in TE-1 cells of esophageal carcinoma cell line, and negatively expressed in HEEp cells of normal esophageal epithelial cell line. Immune histochemical method showed that RAD51, XRCC4 protein expression in esophageal squamous carcinoma tissue, compared with the tissue adjacent to carcinoma and paired cancer metastasis lymph nodes, the difference is statistically significant (P＜0.05), in addition to RAD51 protein positive expression rate in women than men (P＜0.05), and the positive expression rate in other clinical pathological features such as tumor diameter, infiltrating depth and differentiation degree, p-TNM stage had no obvious difference in values (P＞0.05). There was no significant difference in PFS between patients with RAD51 and XRCC4 positive expression and patients with negative expression (all P＞0.05). Conclusion RAD51 and XRCC4 may participate in the occurrence and development of esophageal squamous cell carcinoma by participating in DNA double-strand damage repair, but the specific mechanism remains to be further studied.