The article reviews recent advancements in systemic treatments for advanced hepatocellular carcinoma (HCC). HCC, a significant cause of cancer-related deaths, is often associated with chronic liver disease, metabolic dysfunction, and chronic alcoholism. Conventional chemotherapy is rarely used due to drug resistance and liver dysfunction. Instead, immunotherapy, tyrosine kinase inhibitors (TKIs), and vascular endothelial growth factor (VEGF) inhibitors are commonly employed. Immune checkpoint inhibitors, such as those targeting PD-1 and CTLA-4, have shown promising results in clinical trials, with atezolizumab plus bevacizumab and tremelimumab plus durvalumab emerging as preferred first-line treatments. The article also discusses ongoing clinical trials evaluating combination therapies, including three-drug regimens, CAR T-cells, bispecific antibodies, and targeted agents. The future of HCC treatment may lie in finding synergistic combinations of therapies to overcome drug resistance and improve outcomes.The article reviews recent advancements in systemic treatments for advanced hepatocellular carcinoma (HCC). HCC, a significant cause of cancer-related deaths, is often associated with chronic liver disease, metabolic dysfunction, and chronic alcoholism. Conventional chemotherapy is rarely used due to drug resistance and liver dysfunction. Instead, immunotherapy, tyrosine kinase inhibitors (TKIs), and vascular endothelial growth factor (VEGF) inhibitors are commonly employed. Immune checkpoint inhibitors, such as those targeting PD-1 and CTLA-4, have shown promising results in clinical trials, with atezolizumab plus bevacizumab and tremelimumab plus durvalumab emerging as preferred first-line treatments. The article also discusses ongoing clinical trials evaluating combination therapies, including three-drug regimens, CAR T-cells, bispecific antibodies, and targeted agents. The future of HCC treatment may lie in finding synergistic combinations of therapies to overcome drug resistance and improve outcomes.