These data indicate that: (i) YAP, an oncogene in CCA, up-regulates FGFR1, -2, and -4; (ii) FGFR2 stimulation by FGF5 in turn up-regulates YAP in a feed-forward manner; and (iii) pan-FGFR inhibition causes cell death in vitro and in vivo in YAP-positive CCA cell lines and tumors, likely due to cellular Mcl-1 depletion. Here, FGFR2 is linked to cholangiocarcinoma.