Objective:To investigate the expression and clinicopathologic significance of PHLPP1 and PHLPP2 in esophageal intraepithelial neoplasia and esophageal squamous cell carcinoma (ESCC). Methods:qRT-PCR was used to quantify PHLPP1 and PHLPP2 mRNA expression in 40 pairs of esophageal intraepithelial neoplasia and their matched normal tissues,and 63 pairs of ESCC tissues and their matched normal esophageal tissues. The association of PHLPP1 and PHLPP2 expression with the clinicopathologic features was evaluated in 103 cases of esophageal intraepithelial neoplasia and ESCC patients. Results:The mRNA expression of PHLPP1 and PHLPP2 was significantly downregulated in ESCC tissue samples compared to the matched normal tissues and intraepithelial neoplasia tissues (P < 0.05). Levels of PHLPP1 or PHLPP2 mRNA had no significantly change in esophageal intraepithelial neoplasia compared to their matched normal tissues (P > 0.05). PHLPP1 and PHLPP2 were expressed at relatively high levels in ESCC with an early pathological grade (Ⅰ/Ⅱ),and markedly decreased in Grade III tumors (P < 0.01). In addition,the expression of PHLPP1 and PHLPP2 between patients with TNM stage Ⅰ/Ⅱ and stage Ⅲ of ESCC tissues was statistically significant (P < 0.01). Conclusion:Aberrant expression of PHLPP1 and PHLPP2 was closely related to the development and progression of ESCC. PHLPP1 and PHLPP2 may act as a prognostic marker for this widespread disease.