<h4>Background</h4>This study aimed to develop and validate a novel risk prediction model for hepatorenal syndrome (HRS) in hepatic failure (HF) patients by integrating glucose-6-phosphate dehydrogenase (G6PD) activity with conventional hepatic and renal function biochemical parameters, thereby enhancing early HRS detection beyond the limitations of traditional indicators.<h4>Methods</h4>We performed a retrospective analysis of 264 HF patients (82 with HRS, 182 without HRS) hospitalized between July 2020 and July 2022. Here, G6PD is linked to liver failure.