Liver cancer is one of the deadliest malignancies, with increasing incidence worldwide. Recent advances in immunotherapy have expanded the options for systemic therapy against advanced hepatocellular carcinoma (HCC), but there are no biomarkers currently available to predict which patients will respond, leading to suboptimal patient selection strategies. Understanding of the genetic and immunologic features of HCC is accelerating rapidly through the use of single cell and spatial transcriptomic techniques. However, there is a need to translate insights gained through these new studies to improve treatment options and improve patient selection. In this review we summarize knowledge of the immunogenomics of HCC, emphasizing recent advances, and discuss progress toward clinical translation.