Background: Recent studies have borne out claims that inflammation has a vital role in the development and progression of many diseases, including cancers. It has been reported that neutrophil-lymphocyte ratio (NLR) and red blood cell distribution width (RDW) could act as independent prognostic factors for several malignant tumors. We evaluated the diagnosis and prognosis values of preoperative inflammatory indicators, including NLR and RDW in esophageal cancer (EC). Methods: We retrospectively analyzed the clinical data of 354 EC patients and 220 early esophageal cancer (EEC) undergoing potentially curative esophagectomy in Shandong Provincial Hospital Affiliated to Shandong University and chose 201 age and sex-matched healthy volunteers as the control group. We compared the clinicopathological features, survival curves and prognosis of the EC patients between the high and low groups according to the cutoff values of NLR and RDW. Results: Significant higher preoperative NLR and RDW values were detected in patients with EEC and EC compared to the healthy controls (P <.001). A high RDW was significantly associated with an older age (P <.05). NLR and RDW values after surgery in EC group were significantly higher than those before surgery (P <.001 and P <.001, respectively). For EEC group, a higher RDW value showed a significantly worse overall survival (OS) and disease-free survival (DFS) (P =.040 and P =.013, respectively). For EC group, an increased NLR indicated a significantly association with poor overall survival (OS) (P =.004) and DFS (P =.001). Preoperative NLR can act as an independent prognostic indicator for EC. Conclusion: The preoperative NLR and RDW are convenient, practical easily measured biomarkers of clinical diagnosis and prognostic assessment of patients with EC. Furthermore, NLR was more effective than RDW acting as an independent prognostic biomarker for EC.