BACKGROUND: The cost effectiveness of atezolizumab plus bevacizumab (atezo-beva) versus nivolumab treatment for advanced or unresectable hepatocellular carcinoma is still uncertain. In this study, the cost effectiveness of these treatments was assessed in the United States. METHODS: A cost-effectiveness analysis integrating a network meta-analysis framework was performed using data from the IMbrave150 (ClinicalTrials.gov identifier NCT03434379) and CheckMate 459 (ClinicalTrials.gov identifier NCT02576509) trials. In total, 1244 patients were enrolled. A partitioned survival model was used to evaluate cost effectiveness. A deterministic one-way sensitivity analysis and probabilistic sensitivity analyses were further performed to evaluate model robustness. Subgroup analyses were also performed. RESULTS: Compared with the outcomes using nivolumab, the hazard ratio (HR) for overall survival with atezo-beva was 0.68 (95% CI, 0.48-0.98), and the HR for progression-free survival was 0.63 (95% CI, 0.47-0.85). Atezo-beva treatment was associated with an increase of 1.13 life-years and an increase of 0.69 quality-adjusted life-years (QALYs), as well as a $78,280 increase in cost per patient. The incremental cost-effectiveness ratio was $113,892 per QALY. The incremental net health benefit and the incremental net monetary benefit were 0.17 QALYs and $24,770, respectively, at a willingness-to-pay (WTP) threshold of $150,000 per QALY. The model was most sensitive to the HR for progression-free survival. The probability of atezo-beva being considered cost effective was 78%, and it was >50% in most of the subgroups at the WTP threshold of $150,000 per QALY. CONCLUSIONS: At a WTP threshold of $150,000 per QALY and under current drug pricing, atezo-beva is likely considered cost-effective as a first-line treatment for advanced or unresectable hepatocellular carcinoma compared with nivolumab.