We demonstrate here that FGFR4 is required for FGF19-mediated liver tumorigenesis in vivo and show that treatment with an FGFR4 neutralizing antibody inhibited FGFR4-mediated signaling, proliferation, and colony formation in cell-based assays and tumor growth in preclinical models of HCC in vivo. The gene discussed is FGF19; the disease is hepatocellular carcinoma.