Hepatocellular carcinoma (HCC) remains the sixth most commonly diagnosed malignancy worldwide, still representing an important cause of cancer-related death. Over the next few years, novel systemic treatment options have emerged. Among these, immune checkpoint inhibitors (ICIs) have been widely evaluated and are under assessment, as monotherapy or in combination with other anticancer agents in treatment-naïve and previously treated patients. In particular, the approval of the PD-L1 inhibitor atezolizumab plus the antiangiogenic agent bevacizumab as front-line treatment for advanced HCC has led to the adoption of this combination in this setting, and the IMbrave 150 phase III trial has established a novel standard of care. However, several questions remain unanswered, including the identification of reliable predictors of response to ICIs in HCC patients. In the current paper, we will provide an updated overview of potentially useful predictive biomarkers of response to immunotherapy in advanced HCC. A literature search was conducted in September 2021 of Pubmed/Medline, Cochrane library and Scopus databases.