OBJECTIVE: To assess the impact of albumin (Alb) administration on the prognosis of patients with acute kidney injury (AKI). METHODS: Clinical data of AKI patients in the intensive care unit (ICU) were retrospectively analyzed from the American Medical Information Mart of Intensive Care-IV (MIMIC-IV), including demographic data, acute physiology score (APS), comorbidities, vital signs, laboratory indicators, treatment status, ICU length of stay, and outcome indicators. The main outcome measure is ICU mortality. AKI patients were divided into Alb infusion group and Alb non infusion group based on whether they received Alb treatment. Multiple imputation was used to process missing data and eliminate variables that missing more than 30%. To ensure the stability of the results, propensity score matching (PSM) and inverse probability weighting (IPW) were used to correct the results. Using Kaplan-Meier survival curve and Cox proportional hazards regression model to evaluate the effect of Alb infusion on ICU survival rate in AKI patients. Perform subgroup analysis based on patient age, gender, and comorbidities to evaluate the prognostic effects of Alb on different patient subgroups. RESULTS: A total of 6 390 AKI patients were included, including 1 721 in the Alb infusion group and 4 669 in the Alb non infusion group. After adjusting for key covariates in the Cox regression model, compared with the Alb non infusion group, patients in the Alb infusion group were significantly younger in age, with APS III score, proportion of vasoactive drugs and continuous renal replacement therapy (CRRT) use, sepsis proportion, heart rate, respiratory frequency, aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatinine (Cr), lactic acid (Lac), and arterial partial pressure of carbon dioxide (PaCO) levels significantly higher. The proportion of hypertension, myocardial infarction, and congestive heart failure, as well as blood pressure, urine output, platelet count (PLT), and Alb levels were significantly lower. The results of univariate and multivariate Cox regression analysis on the raw data showed that the risk of death in the Alb infusion group was significantly lower than that in the Alb non infusion group [hazard ratio (HR) = 0.69, 95% confidence interval (95%CI) was 0.60-0.80, all P < 0.05]. The results after propensity score matching (PSM) and inverse probability weighting (IPW) processing are consistent with the original data trend (both P < 0.05). The Kaplan-Meier survival curve showed that the cumulative survival rate during ICU stay in the Alb infusion group was significantly higher than that in the Alb non infusion group (24.48% vs. 12.17%, Log-Rank test: χ = 74.26, P < 0.05). Subgroup analysis shows that Alb infusion has a more significant survival benefit for AKI patients who use vasoactive drugs, have concurrent sepsis, and do not have liver disease. CONCLUSION: Albumin infusion can decrease the ICU mortality of AKI patients.