Objective To evaluate the prognostic factors of patients with non-operative esophageal squamous cell carcinomas(ESCC)and provide the optimal strategy for non-operative ESCC. Methods A prospective study was conducted. A total of 362 primary non-operative ESCC patients were enrolled from October 2009 to November 2014. The cumulative survival rate was calculated by Kaplan-Meier method. Candidate variables were selected by using log-rank test,then Cox proportional hazard model was used for multivariable analysis. Results The median survival time was 17 months, and 1, 3, 5-year survival rates were 64.3%, 25.2%, 16.2%, respectively. Univariate analysis showed the BMI, KPS, TNM stage, and treatment method were closely associated with the prognosis(P<0.05). The Cox regression analysis showed that normal BMI(HR=0.74,95%CI:0.56～0.98), KPS<70(HR=2.62,95% CI: 1.63～4.23), Ⅲ/Ⅳ stage(HR=1.34,95%CI:1.00～1.81),and concurrent chemoradiotherapy(HR=0.64,95%CI:0.43～0.96)were significant predictors of survival. Conclusions The prognostic factors of non-operative treatment of ESCC include BMI, KPS, TNM stage, and treatment method. Concurrent chemoradiotherapy is associated with better survival for non-operative ESCC patients.