Abstract: Objective: This study aimed to evaluate the cost–effectiveness of durvalumab combined with tremelimumab versus sorafenib as the first-line treatment for advanced unresectable hepatocellular carcinoma (uHCC) from the perspective of China’s healthcare system. Methods: Utilizing data from the HIMALAYA clinical trial, a partitioned survival model was developed to simulate clinical pathways, costs, and outcomes. Incremental cost‒effectiveness ratios (ICERs) were calculated through cost‒utility analysis, with robustness assessed via one-way and probabilistic sensitivity analyses. Results: Total costs for the durvalumab‒tremelimumab regimen reached 152,729.04 USD (1.96 quality-adjusted life years, QALYs), whereas they reached 147,406.75 USD (1.48 QALYs) for sorafenib. The ICER of 11,027.79 USD per QALY remained substantially below China’s willingness-to-pay (WTP) threshold of 36,622.13 USD per QALY. Sensitivity analyses confirmed tremelimumab pricing and discount rates as primary determinants of cost‒effectiveness. Conclusion: Within China’s healthcare framework, durvalumab‒tremelimumab is cost effective as a first-line therapy for uHCC, contingent on formulary inclusion and price adjustments.