PURPOSE: This study aims to investigate liver function changes in hepatocellular carcinoma (HCC) patients treated with transcatheter intra-arterial therapy plus molecular targeted agents and programmed cell death-1 (ligand-1) inhibitors, and evaluate the prognostic significance of the combination of Child-Pugh (CP) class and albumin-bilirubin (ALBI) grade (CP/ALBI). METHODS: This is a retrospective study. A total of 149 patients from 2019 to 2023 in China were included. Changes in CP score, ALBI grade, and CP/ALBI grade at 4-8 weeks, 12-16 weeks, and 20-28 weeks post-treatment was evaluated. Cox regression models identified prognostic factors for overall survival (OS) and progression-free survival (PFS). The discrimination of the scoring systems was determined by concordance index (C-index) and time-dependent area under the receiver operating characteristic curve (AUC). RESULTS: Among CP-A patients (n = 137), 11.68% (n = 16) progressed to CP-B by 20-28 weeks ( CONCLUSION: A small but notable proportion of HCC patients experienced liver function deterioration within 28-week of combined treatment. Dynamic monitoring of CP/ALBI grade provides valuable prognostic insights for patient stratification.