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The aim of this study was to examine TP53 gene deletion in esophageal cancer (EC) tissues obtained from patients and to evaluate its clinical significance. Forty surgical specimens from patients with esophageal squamous cell carcinoma were examined for TP53 gene deletion using the fluorescence in situ hybridization (FISH) technique. Thirty-two male and 8 female patients were enrolled, with an average age of 56 years. TP53 gene deletion was significantly higher in poorly-differentiated EC cases compared to well-differentiated cases (P=0.028). The TP53 gene deletion rate was also significantly higher in the group with lymph node metastasis compared to the group without lymph node metastasis (P=0.0313). The TP53 gene deletion rate was shown to be correlated with the level of differentiation and lymph node metastasis in EC; it may therefore be an important molecular marker for evaluating the condition of EC in patients.