The uses of molecular targeted therapy and immunotherapy are without a doubt the hottest topics of therapeutic research for the treatment of hepatocellular carcinoma (HCC) in recent years and are expected to continue in the near future. In 2007, sorafenib became the first-line therapy for progressive HCC, while, after nearly a decade of extensive exploration in 2018, lenvatinib became the second approved first-line treatment for progressive HCC in China. In 2017 and 2018, the US Food and Drug Administration (FDA) approved nivolumab and pembrolizumab as second-line therapy for HCC, respectively, thus paving the way to a new era of immunotherapy use.