Hepatocellular carcinoma is a worldwide common cancer with the fourth leading cause of cancer-related death [1,2]. Although the surgical resection, radiofrequency ablation or liver transplantation may be curative for early-stage disease, the vast majority of patients have existed with advanced, unresectable disease at initial diagnosis and present a poor prognosis [3,4]. The systemic therapy is the therapeutic cornerstone for advanced hepatocellular carcinoma. The multikinase inhibitors represented by sorafenib and lenvatinib, which target angiogenesis mainly driven by VEGF, have been approved for the first-line systemic treatment regimens for patients with advanced hepatocellular carcinoma [5–8].