Our data indicate that a) YAP is critical for dietary PA‐enhanced metastasis; b) PA functions as an upstream signaling molecule to drive the ZDHHC15‐YAP loop, promoting metastasis in breast and ovarian cancers; c) PA promotes ZDHHC15‐mediated KIBRA palmitoylation, which affects KIBRA protein stability, subcellular localization, and activity toward YAP transcription; d) pharmacological inhibition of the ZDHHC15‐YAP loop and fatty acid synthesis suppresses PA‐promoted metastasis formation in mice. Here, WWC1 is linked to ovarian cancer.