Background and Aims Currently, there are multiple assessment systems available for evaluating prognosis indicators in liver cancer, each with its own strengths and limitations. Joint assessment may enhance predictive efficiency. Therefore, this study was conducted to investigate the predictive value of the combination of age-adjusted Charlson complication index (aCCI), tumor burden score (TBS), and albumin-bilirubin (ALBI) score (aCTA score), integrating complications, morphological features, and liver function, in predicting post-hepatectomy liver failure (PHLF). Methods The clinical data of 236 patients with primary liver cancer undergoing hepatectomy in Renmin Hospital of Wuhan University from January 2020 to February 2023 were retrospectively collected. Patients were divided into the PHLF group (19 cases) and non-PHLF group (217 cases) based on the occurrence of liver failure within 1 week after surgery. Univariate and multivariate Logistic regression analyses were conducted to identify the independent risk factors for PHLF. Receiver operating characteristic (ROC) curves were used to evaluate the predictive performance of the combined indicators. A weighted risk score for PHLF was constructed using the Framingham Research Center Logistic model. Internal validation was performed using the concordance index (C-index), ROC curves, and calibration curve. The clinical utility of the score was assessed using decision curve analysis (DCA). Results Among the 236 patients undergoing liver resection for liver cancer, 19 cases (8.1%) developed PHLF. Multivariate Logistic regression analysis revealed that aCCI ( OR=1.557, 95% CI=1.014-2.391, P=0.043), TBS ( OR=1.214, 95% CI=1.022-1.442, P=0.027), and ALBI ( OR=5.387, 95% CI=1.844-15.733, P=0.002) were independent risk factors for PHLF in liver cancer patients (all P<0.05). The area under ROC (AUC) for aCCI, TBS, ALBI, and the combination of the three scoring systens were 0.662, 0.733, 0.768, and 0.822, respectively. Based on aCCI, TBS, and ALBI, the jointly constructed aCTA scoring system (with a maximum score of 10) had a C-index of 0.828 (95% CI=0.732-0.925). and the AUC was 0.809 ( P<0.05), indicating good discriminative ability. The calibration curve showed close agreement between predicted and observed values, suggesting good accuracy of the score. DCA demonstrated a net benefit for patients from the aCTA score model, indicating its good clinical applicability. Conclusion aCCI, TBS, and ALBI are independent risk factors for PHLF in liver cancer patients. The aCTA score, constructed based on them, has good predictive value and clinical guidance for high-risk patients.