The landscape of liver cancer treatment is changing rapidly, but the best sequence of treatment remains unclear. Immunotherapy-based combinations have rapidly become the dominant first-line treatment for advanced hepatocellular carcinoma (HCC). However, realistic treatment outcomes are severely limited by liver function and comorbidity burden. Hepatocellular carcinoma is one of the most common malignancies with increasing incidence and accounts for approximately 90% of primary liver tumors. In North America, Europe and Japan, hepatitis C virus infection together with alcohol use is the main risk factor. Previously, sorafenib was the standard first-line treatment, regorafenib the second-line choice, with a median progression-free survival of 3.1 months versus 1.5 months for placebo. Currently, immunotherapy represents an adequate treatment option along with cabozantinib and ramucirumab in the second-line setting. Treatment options are limited by liver function according to the Child-Pugh classification and involve a multidisciplinary approach[1][2][3].