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Background: Many complications after hepatectomy can lead to perioperative death, among which posthepatectomy liver failure (PHLF) is the leading one. Existing studies suggest that one of the most important risk factors for PHLF is cirrhosis. Hepatitis B virus (HBV) infection is an important factor in the occurrence of cirrhosis, and the exact relationship between HBV infection and PHLF is not obvious. Diabetes mellitus and postoperative blood glucose are closely associated with liver regeneration, but its exact relationship with PHLF remains unclear., Methods: We collected clinical indicators from 920 adult patients treated at the Liver Surgery and Transplantation Center of West China Hospital of Sichuan University from April 2009 and April 2019. We conducted a univariate analysis find out the risk factors of PHLF, follow by a multivariate analysis to ascertain the independent risk factors. Receiver operating characteristic (ROC) curves were plotted to evaluate the predictive efficiency of each risk factor., Results: Following hepatectomy, 205 (22.2%) of patients were diagnosed with PHLF. Several variables were confirmed to related with PHLF significantly: diabetes [P<0.01, odds ratio (OR) =10.845, 95% confidence interval (CI): 5.450-21.579], HBV (P<0.01, OR =0.345, 95% CI: 0.187-0.635), blood glucose on the first postoperative day (post-BG1) (P=0.027, OR =1.059, 95% CI: 1.006-1.115), blood glucose on the third postoperative day (post-BG3) (P=0.021, OR =1.085, 95% CI: 1.012-1.162), blood glucose on the fifth postoperative day (post-BG5) (P=0.014, OR =1.119, 95% CI: 1.023-1.225), postoperative total bilirubin (post-TB) (P<0.01, OR =1.160, 95% CI: 1.133-1.187), and liver cirrhosis (P<0.01, OR =0.982, 95% CI: 0.561-1.717) identified to be independent risk factors of PHLF., Conclusions: Diabetes, HBV, post-BG1, post-BG3, and post-BG5 are related to the development of PHLF, and diabetes and post-BG can be used as predictors of the development of PHLF in patients with hepatocellular carcinoma (HCC)., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://dx.doi.org/10.21037/jgo-21-491). The authors have no conflicts of interest to declare., (2021 Journal of Gastrointestinal Oncology. All rights reserved.)