**Abstract**

Hepatocellular carcinoma (HCC) is a highly prevalent primary liver carcinoma and the main cause of deaths (linked with cancer) across the globe. Despite advancements in prevention strategies, testing, and technological advances in diagnosis and treatment, the occurrence and fatality rate of HCC continue to rise. In recent decades, the approval of immune checkpoint inhibitors (ICIs) has transformed palliative treatment for liver cancer. However, the majority of patients with liver cancer do not respond to these treatments. Herein, we elaborated the microenvironment of the liver cancer and candidate immunotherapies based on activating the antitumor activity of myeloid, NK and T cells, chimeric antigen receptors-T or -NK cells, vaccines, oncolytic viruses, and combination therapies, as well as the challenges and opportunities of immunotherapies in liver cancer. This review also explores the rationale, molecular foundation, and supporting preclinical evidence for immunotherapies in HCC, available clinical evidence, and current immunotherapeutic clinical studies.

**Keywords:** hepatocellular carcinoma, tumor-immune microenvironment, locoregional treatment, liver cirrhosis, systemic treatment
