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Background Acute kidney injury (AKI) is the most common cause of organ failure in multiple organ dysfunction syndrome (MODS) and is associated with increased mortality. This study aimed at determining the efficacy of sequential organ failure assessment (SOFA), and acute physiology and chronic health evaluation II (APACHE-II) scoring systems in assessing the prognosis of critically ill patients with AKI undergoing continuous renal replacement therapy (CRRT). At present, APACHE-II score and SOFA score were also used to evaluate and predict the prognosis of critically ill patients with AKI. Methods The predictive value of SOFA and APACHE-II scores for 28- and 90-d mortality in patients with AKI undergoing CRRT were determined by multivariate analysis, sensitivity analysis, and curve-fitting analysis. Results A total of 836 cases were included in this study. Multivariate Cox logistic regression analysis showed that SOFA scores were associated with 28- and 90-d mortality in patients with AKI undergoing CRRT. The adjusted HR of SOFA for 28-d mortality were 1.18 (1.14, 1.21), 1.24 (1.18, 1.31), and 1.19 (1.13, 1.24) in the three models, respectively, and the adjusted HR of SOFA for 90-d mortality was 1.12 (1.09, 1.16), 1.15 (1.10, 1.19), and 1.15 (1.10, 1.19), respectively. The subgroup analysis showed that the SOFA score was associated with 28-d and 90-d mortality in patients with AKI undergoing CRRT. APACHE-II score was not associated with 28- and 90-d mortality patients with AKI undergoing CRRT. Curve fitting analysis showed that SOFA scores increased had a higher prediction accuracy for 28- and 90-d than APACHE-II. Conclusions The SOFA score showed a higher accuracy of mortality prediction in critically ill patients with AKI undergoing CRRT than the APACHE-II score.