Background: Acute kidney injury (AKI) is a common complication after pediatric cardiac surgery. And autologous blood transfusion (ABT) is an important predictor of postoperative AKI. Unlike previous studies, which mainly focused on the correlation between ABT and AKI, the current study focuses heavily on the causal relationship between them, thus providing guidance for the treatment of patients during hospitalization to reduce the occurrence of AKI. Methods: A retrospective cohort of 3386 patients extracted from the Pediatric Intensive Care database was used for statistical analysis, multifactorial analysis, and causal inference. Characteristics that were correlated with ABT and AKI were categorized as confounders, instrumental variables, and effect modifiers, and were entered into the DoWhy causal inference model to determine causality. The calculated average treatment effect (ATE) was compared with the results of the multifactorial analysis. Results: The adjusted odds ratio (OR) for ABT volume was obtained by multifactorial analysis as 0.964. The DoWhy model refute test was able to indicate a causal relationship between ABT and AKI. Any ABT reduces AKI about 15.3%–18.8% by different estimation methods. The ATE regarding the amount of ABT was –0.0088, suggesting that every 1 mL/kg of ABT reduced the risk of AKI by 0.88%. Conclusions: Intraoperative transfusion of autologous blood can have a protective effect against postoperative AKI.