Abstract: Objective To evaluate the predictive value of neutrophil-to-lymphocyte ratio (NLR) and hemoglobin-to-white blood cell ratio (HWR) prior to treatment in prognosis of non-operative esophageal squamous cell carcinoma (ESCC) patients. Methods From October 2009 to November 2014, a total of 362 non-operative ESCC patients were enrolled in this prospective study. χ² test was used to analyze the relationship between NLR, HWR and general clinical features; Univariate and multivariate Cox regression analysis was performed to evaluate the association between variables and prognosis of non-operative ESCC patients. Results The optimal cutoff level of 1.23 for NLR and 24.92 for HWR were identified by X-title software. χ² test indicated NLR was significantly associated with gender, tumor length, T stage, TNM stage and fasting blood glucose level. Moreover, univariate and multivariate analyses showed that high NLR and high HWR were all associated with a poor prognosis in non-operative ESCC. However, when patients were specifically stratified by treatment modus, subset analysis showed that NLR was only predictive of prognosis in the concurrent chemoradiotherapy group (HR=4.080,95% CI:1.074-15.497,P=0.039), whereas the influence of HWR on prognosis was just existed in the sequential chemoradiotherapy group (HR=2.625,95% CI:1.311-5.254,P=0.006). Conclusions In this investigation, we found that high NLR and high HWR were associated with poor prognosis in non-operative ESCC.