Advanced hepatocellular cancer (HCC) is the fourth most common cause of cancer death. Two of the major HCC characteristics are neoangiogenesis and the immune suppression within its limits. Indeed, chronic inflammation promotes vascular alterations by producing several angiogenic factors. Cancer and stromal cells, together with the angiogenic factors, guide the development of a tumor immunosuppressive microenvironment by recruiting regulatory T cells, upregulating the expression of immune checkpoint molecules, and exhausting effector T cells. On this basis, anti-angiogenic therapy has taken on a predominant role in the treatment of HCC, however, it only had a limited impact on overall survival. In this scenario, the combination of immunotherapy and anti-angiogenic therapy could represent a promising novel therapeutic strategy. Recently, atezolizumab plus bevacizumab has been approved as the first-line standard of care thanks to the IMbrave 150 trial results. Data from other ongoing trials could drastically change the clinical approach to HCC treatment.