INTRODUCTION: Many clinical trials have been conducted with chemotherapies in 
patients with advanced hepatocellular carcinoma (HCC). However, few agents have 
shown efficacy. It is thought that the efficacy of some agents might have 
resulted from the heterogeneity of tumors, insufficient dosages due to liver 
cirrhosis, and post-therapy effects. In recent years, immune checkpoint 
inhibitors have shown promising clinical activity and safety in patients with 
advanced HCC.
AREAS COVERED: The authors provide an overview of chemotherapies used for the 
treatment of HCC, including ongoing trials. The authors also provide their 
expert opinion on the subject area and provide their future perspectives.
EXPERT OPINION: Based on favorable phase III clinical trial data, sorafenib and 
lenvatinib are considered promising agents for HCC as first-line systemic 
chemotherapy. Moreover, regorafenib and cabozantinib are useful second-line 
therapies after the failure of sorafenib. Furthermore, in early phase clinical 
trials, immune checkpoint inhibitors and the combinations of these inhibitors 
and molecular targeted agents have demonstrated promising activity. Therefore, 
better survival results are expected from future phase III clinical trials.