We found LIF, but not IL-6, suppressed Hippo pathway in human PDAC cells, as evidenced by increased YAP/TAZ-TEAD transactional activities and increased expression of YAP1-targeted genes CNTF and ANKRAD. Neutralization of LIF or LIF knockdown led to increased phosphorylation of YAP at Ser127 in both human and mouse pancreatic cancer cell lines. Here, CNTF is linked to familial pancreatic carcinoma.