Our in vitro and in vivo models demonstrate that circUCK2(2,3) enhances HCC cell proliferation, migration, and invasion, and increases the sensitivity of HCC cells to the cytotoxicity of EGFR inhibitors, as well as the synergistic cytotoxic effect of lenvatinib combined with EGFR inhibitors. This evidence concerns the gene EGFR and hepatocellular carcinoma.