Abstract: Objective To study the relation between 14-3-3ζ and p-Akt expression and esophageal squamous carcinoma. Methods Expressions of 14-3-3ζ and p-Akt in esophageal squamous carcinoma and its adjacent tissues were detected by immunohistochemistry. Results The expression level of 14-3-3ζ and p-Akt was higher in esophageal squamous carcinoma tissue than in its adjacent normal tissue, and was closely related with the histological differentiation and lymphatic metastasis but not related with the age of patients and the tumor invasion depth. Spearman correlation analysis showed that the expression level of 14-3-3ζ and p-Akt was significantly related with esophageal squamous carcinoma. Conclusion 14-3-3ζ and p-Akt are involved in the occurrence and development of esophageal squamous carcinoma.