Objective: Hypoxic-ischemic encephalopathy (HIE) frequently leads to neurological complications, such as seizures and developmental disorders. In addition to these challenges, many infants with HIE experience multi-organ dysfunction, and HIE is a major cause of acute kidney injury (AKI) during the neonatal period. This study aimed to investigate the risk factors for AKI in neonates treated with therapeutic hypothermia (TH) for HIE. Methods: We retrospectively reviewed neonates who received TH for HIE at a single center between January 2015 and August 2024. AKI was defined according to the neonatal modified Kidney Disease Improving Global Outcome criteria. Initial blood gas analysis, seizures, severity of HIE, neurologic studies, and mortality were compared between infants with and without AKI. Results: Among 288 neonates with HIE, TH was performed on 60 neonates, of which 3 were excluded, resulting in a total of 57 neonates. A total of 25 patients (43.9%) developed AKI, of whom 10 had stage 1 AKI, 6 had stage 2 AKI, and 9 had stage 3 AKI. In stage 3 AKI, one patient (1.8%) needed renal replacement therapy. Initial pH (P=0.040) and base excess (BE) (P=0.008) were significantly lower in the AKI group compared to the non-AKI group. AKI patients had a significantly higher rate of s...