Fibroblast growth factor receptor 4 (FGFR4) is a member of the fibroblast growth factor receptor family, which is closely related to the occurrence and development of hepatocellular carcinoma (HCC). In this article, a series of indazole derivatives were designed and synthesized by using computer-aided drug design (CADD) and structure-based design strategies, and then they were evaluated for their inhibition of FGFR4 kinase and antitumor activity. F-30 was subtly selective for FGFR4 compared to FGFR1; it affected cell growth and migration by inhibiting FGFR4 pathways in HCC cell lines in a dose-dependent manner.