Objective To investigate the prognostic significance of prognostic nutritional index in patients with esophageal squamous cell carcinoma (ESCC) surgery and its correlation with systemic inflammatory response markers. Methods A retrospective analysis of the clinical data of patients with esophageal squamous cell carcinoma who underwent radical esophageal cancer surgery at Sichuan Cancer Hospital from December 2017 to October 2018. And calculate the patient′s prognostic nutritional index (PNI), neutrophil⁃to⁃lymphocyte ratio (NLR), lymphocyte⁃to⁃monocyte ratio (LMR), platelet⁃to⁃lymphocyte ratio (PLR) and other indicators. Spearman was used to analyze the correlation between PNI and systemic inflammatory response markers, and Kaplan⁃Meier survival curve and Cox proportional hazard regression model were used to analyze the impact of different PNI levels on the prognosis of patients with esophageal squamous cell carcinoma surgery. Results PNI was positively correlated with LMR (R=0.514, P<0.001), and negatively correlated with NLR (R=-0.401, P<0.001) and PLR (R=-0.591, P< 0.001). Univariate analysis showed that age (P=0.13), LMR (P=0.004), NLR (P=0.018), PNI (P=0.017) were significantly related to the patient′s OS. Further multivariate analysis showed that age (OR=1.676, 95%CI=1.056-2.661, P=0.028) and PNI (OR= 0.589, 95%CI=0.370-0.939, P=0.026) are independent prognostic factors of OS. PNI≥45.26 and age<65 years old indicate a better prognosis for patients undergoing radical esophageal cancer surgery. Conclusion PNI is an important predictor of survival outcome for patients with esophageal squamous cell carcinoma undergoing radical resection of esophageal cancer. It has certain clinical value.