The findings of this study demonstrated that ECM stiffness could affect the phenotype of primary liver cancers and that the YAP1/ABHD11‐AS1/STAU2/ZYX/p‐YAP1 signaling pathway was an entry point that could be used to explore the specific mechanisms of mechanical signal conduction from the ECM in ICC cells and their impact on progression of cancer. Here, ZYX is linked to intrahepatic cholangiocarcinoma.