Objective To investigate the predictive value of soluble growth?stimulated expressed gene 2 protein （sST2） in predicting sepsis?associated acute kidney injury （SA?AKI）. Methods From January 2020 to December 2023， a total of 395 sepsis patients with sepsis from the Emergency Department， Affiliated Hospital of Nantong University were enrolled in this retrospective observational study. These patients were further categorized into two groups： AKI group （114 cases） and non?AKI group （281 cases）. Clinical data and laboratory indicators were collected within 24 hours after admission. ROC curve analysis was used to evaluate the diagnostic ability of sST2 for SA?AKI. Logistic regression analysis was performed to assess independent risk factors for the development of SA?AKI. Concurrently， two predictive models for SA?AKI were constructed， and the predictive ability of sST2 for SA?AKI was assessed using the Area Under the Curve （AUC）， the Net Reclassification Index （NRI） and the Integrated Discrimination Improvement （IDI）. Results T The levels of sST2 were significantly higher in the AKI group compared to the non?AKI group （P < 0.001）. The AUC predicted by sST2 （0.839， 95% CI： 0.799 ~ 0.874） in sepsis patients with AKI was significantly superior to other laboratory indicators （P < 0.000 1）. An sST2 concentration greater than 85 ng/mL independently increased the risk for SA?AKI （OR： 14.315， 95% CI： 5.867 ~ 34.926， P < 0.001）. Incorporating sST2 into the prediction model substantially improved the AUC values （0.954 vs. 0.909， P < 0.000 1）， NRI （21.48%， 95% CI： 11.48% ~ 31.49%， P < 0.000 1） and IDI （8.62%， 95% CI： 5.75% ~ 11.49%， P < 0.000 1）. Conclusion sST2 has the potential to serve as a promising biomarker for prognosticating AKI in septic patients.