To explore the role of CDC25B, PED/PEA-15 in the development of esophageal carcinoma and its influence on the prognosis.Fluorescence quantitative real-time PCR and immunohistochemistry methods were used to analyze the expression of CDC25B, PED/PEA-15 in esophageal carcinoma. Moreover, survival analysis was done using the Kaplan-Meier method.In 66 cases of esophageal cancer tissues, the relative content of CDC25B mRNA was 16.22 (13.93-18.90). The positive expression rate of CDC25B protein was 48.5%, significantly higher than normal mucosa tissues (0%) (p<0.01). The relative content of PED/PEA-15 mRNA was 12.47 (10.41-14.93). The positive expression rate of PED/PEA-15 protein was 68.2%, significantly higher than normal mucosa tissues (17.6%) (p<0.01). The CDC25B protein expression was correlated with differentiation grade and depth of invasion (p<0.05). The PED/PEA-15 protein expression was related to differentiation grade, lymph node metastasis, and depth of invasion (p<0.05). Survival analysis showed that the mean survival time of PED/PEA-15-positive expression group was lower compared with the negative expression group (χ(2)=5.549, p=0.018). Analysis of the relationship between CDC25B and PED/PEA-15 suggested that there was a positive correlation between them (r=4.061, p=0.044).Both CDC25B and PED/PEA-15 play a certain role in the carcinogenesis of esophageal cancer, and PED/PEA-15 has a greater influence on postoperative survival time. They will be the new diagnostic/therapeutic targets in esophageal carcinoma.