Background and objective <p>Post-hepatectomy liver failure (PHLF) is one of the major complications following hepatectomy for hepatocellular carcinoma (HCC). Early identification and precise prediction of PHLF are essential for effective management. This study aimed to evaluate the predictive value of intra-hepatectomy indocyanine green retention rate at 15&#xa0;min (ICGR15) for the remnant liver for grade B/C PHLF in HCC patients undergoing hemi-hepatectomy.</p> Methods <p>This prospective study recruited 31 HCC patients who underwent hemi-hepatectomy. ICGR15 was measured at three time points: pre-hepatectomy, intra-hepatectomy (for the remnant liver), and post-hepatectomy. The primary endpoint was the occurrence of grade B/C PHLF according to ISGLS criteria. Logistic regression analysis was employed to evaluate the predictive performance of each parameter and to conduct risk assessment. The XGBoost algorithm was utilized to compare the predictive values of various parameters by calculating the mean Shap values.</p> Results <p>Among the study participants, 25.8% (8 patients) developed grade B/C PHLF. The intra-hepatectomy ICGR15 for remnant liver exhibited the highest predictive accuracy for grade B/C PHLF, with a ROC-AUC of 0.864 and a PR-AUC of 0.791. The optimal threshold for ICGR15-intra was established at 19.8%. Patients with ICGR15-intra value of 19.8% or higher were found at significantly increased risk of grade B/C PHLF (OR[95% CI] = 3.602[1.437–6.750], <i>P</i> value = 0.004), and experienced a higher incidence of severe post-hepatectomy complications.</p> Conclusion <p>Intra-hepatectomy ICGR15 for the remnant liver was an important predictor of grade B/C PHLF in patients undergoing hemi-hepatectomy for HCC. An intra-hepatectomy ICGR15 threshold of 19.8% might effectively identify patients at high risk of developing grade B/C PHLF and severe post-hepatectomy complications, helping surgeons’ final decision-making on the table.</p>