Objective: To study the expression of CDC20, TOP2A in esophageal squamous cell carcinoma and its relationship with survival of esophageal carcinoma. Methods: 65 patients with esophageal squamous cell carcinoma from January 2016 to June 2018 were selected by computer random selection. All patients were treated with radical operation. The CDC20, TOP2A expression of the patients was examined. At the same time, the relationship between 3-year survival rate and CDC20, TOP2A was analyzed by follow-up investigation. Results: the CDC20, TOP2A expression level of cancer tissue group was higher than that of adjacent tissue group and normal tissue group (P 0.05) and positive proportion in TNM stage, lymphatic metastasis, invasion factor and CDC20, TOP2A expression level; there were differences in tumor differentiation, 5-year survival rate and CDC20, TOP2A expression level (P P >0.05), and showed inverse proportion relationship. Conclusion: metastasis, recurrence and prognosis of esophageal squamous cell carcinoma are related to the level of CDC20,TOP2A expression. These two indexes can effectively evaluate the pathological situation of esophageal cancer and provide an important reference for the prognosis of esophageal squamous cell carcinoma patients.