BACKGROUND/AIM:This study evaluated the clinical significance of baseline lymphocyte-to-monocyte ratio (LMR) and its early dynamic changes as an on-treatment biomarker in patients with advanced hepatocellular carcinoma (HCC) receiving atezolizumab plus bevacizumab (Ate/Bev), with stratification by alpha-fetoprotein (AFP) status. PATIENTS AND METHODS:We retrospectively reviewed 108 patients with advanced HCC treated with first-line Ate/Bev. Baseline LMR and LMR at six weeks (LMR 6w) were calculated. Patients were classified into high/low groups (cutoff: 3.69) and dynamic change groups [increased (Up) vs. decreased (Down)]. Overall survival (OS) and objective response rate (ORR) were assessed according to baseline AFP levels (cutoff: 20 ng/ml). RESULTS:High baseline LMR significantly correlated with longer OS (median not reached vs. 17.3 months, p<0.001). Notably, patients with increased LMR at six weeks (Up group) demonstrated significantly superior OS compared to the Down group (33.6 vs. 18.9 months, p=0.018) and a higher ORR (46.0% vs. 26.0%, p=0.037). The High+Up cohort achieved the most favorable prognosis. In stratified analyses, these prognostic and predictive values of early LMR dynamics were prominently observed in AFP-negative patients (p<0.05), but were attenuated in AFP-positive individuals. CONCLUSION:Early dynamic increase in LMR serves as a powerful, cost-effective on-treatment biomarker for Ate/Bev therapy in advanced HCC. Integrating systemic immune dynamics with tumor biology provides superior risk stratification, particularly for AFP-negative patients.