Objective To evaluate the clinical application value of four inflammatory indices [monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR)] in predicting postoperative mortality risk in patients with Siewert type Ⅱ esophagogastric junction adenocarcinoma, and to explore the predictive performance of four inflammatory indices. Methods This retrospective study collected clinical data from 310 patients with Siewert typeⅡ esophagogastric junction adenocarcinoma who were admitted to the Second Hospital of Lanzhou University between October 2016 and March 2023, and met the inclusion and exclusion criteria. Univariate analysis was used to initially screen variables related to postoperative mortality risk. The variance inflation factor (VIF) analysis was performed to assess multicollinearity issues, and multivariate regression analysis was used to further reveal the independent effects of key variables on postoperative mortality risk. The performance of the predictive models was evaluated using receive operatior characteristic curves and Kaplan-Meier survival analysis, and the effects of different inflammatory indices on patient survival were explored. Finally, machine learning methods such as Light GBM, random forest, support vector machine (SVM), and XGBoost were used to evaluate the predictive performance of the four inflammatory indices. Results The four inflammatory indices were significantly associated with postoperative mortality risk in patients with Siewert type Ⅱ esophagogastric junction adenocarcinoma (MLR: HR=2.6884, 95% CI 1.4559 to 4.9642, P=0.002; PLR: HR=1.0022, 95% CI1.0001 to 1.0043, P=0.041; SII: HR=1.0003, 95% CI1.0001 to 1.0006, P=0.002; NLR: HR=1.0697, 95% CI 1.0277 to 1.1134, P=0.001). Machine learning model results showed that NLR had the best performance in the random forest model, with an AUC of 0.863 in the training set and an AUC of 0.834 in the test set. Conclusion Preoperative clinical indicators, especially the NLR inflammatory factor, are of significant importance in predicting the postoperative mortality risk of patients with Siewert typeⅡ esophagogastric junction adenocarcinoma.