ABSTRACT: Purpose: The purpose of the present study was to investigate the prognostic value of inflammatory and nutritional-based scores, including the albumin/fibrinogen ratio (AFR) and albumin/globulin ratio (AGR), in patients with esophageal squamous cell carcinoma (ESCC). Methods: The medical records of 641 patients with resectable ESCC from our institution were retrospectively analyzed. The preoperative AFR and AGR were investigated based on serum albumin, globulin and plasma fibrinogen levels. X-tile software, Kaplan-Meier survival curves and Cox proportional hazard models were performed to identify their prognostic value. The predictive accuracy was evaluated by the concordance index (C-index), calibration plots, and decision curve analysis (DCA). Results: The optimal cutoff values were 15.3 and 1.8 for AFR and AGR, respectively. Univariate survival analysis identified age, smoking history, tumor size, pT status, pN status, NLR, PLR, fibrinogen, albumin, AFR, and AGR as factors associated with overall survival. Multivariate analysis indicated that preoperative AFR (HR: 0.690, 95% CI = 0.495~0.960, P = 0.028), rather than other inflammation- and nutrition-based scores, was an independent predictor of overall survival. The C-index of the predicted nomogram containing AFR (C-index = 0.677) was higher than that of the nomogram without AFR (C-index = 0.656). The calibration curves showed that the predictive abilities were consistent with the actual observation results. Moreover, compared with the traditional staging system, the results of DCA showed that the nomogram had superior predictive ability and higher clinical utility. Conclusion: Our preliminary study suggested that a low preoperative AFR might be a novel and valuable predictor of poor prognosis in patients with ESCC, which may be helpful for prognosis assessment, patient counseling, and therapeutic modality selection.