In this study, we demonstrated that low RIPK1 or high TLR3 status in tumor tissues was significantly associated with more invasiveness which was also confirmed by subsequent in vitro studies that the stimulation of TLR3 by TLR3 ligand, Poly(I:C) promoted CCA cell invasion in NF-κB and MAPK-dependent manner. This evidence concerns the gene RIPK1 and cholangiocarcinoma.