Background: Postoperative liver failure remains the main complication and predominant cause of hepatectomy-related mortality for patients undergoing liver resection. Aim: Our aim is to investigate whether immediate postoperative Fibrosis-4 could predict postoperative liver failure. Methods: We retrospectively enrolled 1353 consecutive hepatocellular carcinoma patients undergoing radical resection. The characteristics and clinical outcomes were compared between patients with high and low immediate postoperative Fibrosis-4. Risk factors for hepatic failure were evaluated by univariate and multivariate analysis. Results: Using a receiver operating characteristic curve, immediate postoperative Fibrosis-4 showed good prediction ability for postoperative liver failure (AUROC = 0.647, P < 0.001). With the optimal cut-off value of 5.9, the high postoperative Fibrosis-4 group (Fibrosis-4 < 5.9) had higher postoperative complication (39.1% vs 28.6%, P < 0.001), mortality (2.8% vs 0.6%, P < 0.001) and liver failure (13.9% vs 6.2%, P < 0.001). In addition, patients with high Fibrosis-4 had worse and delayed recovery of liver function. By univariate and multivariate analysis, Fibrosis-4, as well as liver removed volume, total bilirubin and albumin was identified as independent risk factor for postoperative liver failure. Conclusions: Immediate postoperative Fibrosis-4 showed good prediction ability for postoperative liver failure, and required measure should be taken to prevent liver failure when high postoperative Fibrosis-4 appeared. (C) 2017 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.