摘要The incidence of hepatocellular carcinoma(HCC)has been increasing for decades.This disease has now risen to become the sixth most common malignancy overall,while ranking as the third most frequent cause of cancer mortality.While several surgical interventions and loco-regional treatment options are available,up to 80％ of patients present with advanced disease not amenable to standard therapies.Indeed,traditional cytotoxic chemotherapeutic agents are notoriously ineffective and essentially play no role in the management of affected patients.This has led to an enormous need for more effective sys-temic therapeutic options.In recent years,immunotherapy has emerged as a potentially viable and exciting new alternative for the treatment of HCC.Although the current immunotherapeutic options remain imperfect,various strategies can be employed to further improve their efficacy.New findings have revealed epigenetic modulation can be effective as a new approach for improving HCC immuno-therapy.Studying the gut microbiome(gut-liver axis)can also be an interesting subject in this regard.Here,we explore the latest insights into the role of immunotherapy treating HCC,both mono and in combination with other agents.We also focus on the impact of epigenetic drugs and the microbiome in the overall effectiveness of HCC immunotherapy.