Objective: To explore the predictive value of systemic immune-inflammation index (SII) and prognostic nutritional index (PNI) for the prognosis in patients with septic shock and acute kidney injury (AKI). Methods: A total of 64 patients with septic shock and AKI who completed treatment at the People"s Hospital of Ningdu County between January 2024 and December 2024 were selected. They were divided into favorable group and adverse group according to the prognosis. The renal function indicators [serum creatinine (Scr) and blood urea nitrogen (BUN)], parathyroid hormone (PTH), blood gas indicators (lactic acid, serum calcium, serum potassium and serum phosphorus), SII and PNI were compared between the two groups. Multivariate logistic regression analysis, Pearson correlation analysis, and the receiver operating characteristic (ROC) curve were used to evaluate the predictive value of SII and PNI for the prognosis in patients with septic shock and AKI. Results: Compared with the favorable group, Scr, BU, PTH, lactic acid, serum calcium, serum potassium, serum phosphorus and SII were significantly higher, and PNI was significantly lower in the adverse group (P<0.05). Multivariate logistic regression analysis showed that SII and PNI were independent influencing factors of the prognosis of septic shock with AKI (P<0.05). Pearson correlation analysis showed that SII was negatively correlated with the prognosis of septic shock with AKI, while PNI was positively correlated with the prognosis (P<0.05). ROC curve analysis showed that the areas under the curve of SII and PNI for predicting the prognosis of septic shock with AKI were 0.725 and 0.875, respectively. Conclusion: SII and PNI have high predictive value for the prognosis of patients with septic shock and AKI, and should be closely monitored in clinical practice.