Hepatocellular carcinoma (HCC) carries an unfavorable prognosis and novel therapeutic strategies are needed. Until now, only few systemic agents have improved survival in patients with advanced stage disease. Immunotherapy changed the landscape in several tumor types by producing unprecedented clinical outcomes with a favorable safety profile. Liver presents a particular immune-suppressive microenvironment and HCC develops in a background of chronic inflammation in the vast majority of cases. In this regard, immunotherapy may be a suitable strategy. Preliminary research focused on therapies involving immune cells and anti-tumor immune response for HCC has shown encouraging preliminary results. Immune checkpoint inhibitors, such the anti-PD-1/PD-L1 monoclonal antibodies, have provided durable responses in patients with advanced stage disease, although the pioneers phase Ⅲ trials did not confirm survival superiority over the available agents. Cancer vaccines, adoptive cellular therapies and combinations of local modalities with immunotherapy are promising approaches under active research.