This review synthesizes current understanding of the non-canonical Hippo pathway’s multilayer regulatory mechanisms in head and neck cancers, highlighting its complex signaling network comprising core kinase components (e.g., TAO, MAP4K, and NDR1/2 kinases), cell polarity regulators (CRUMBS/SCRIBBLE), cell junction modulators (AMOT family), and 14–3-3 scaffold proteins. The gene discussed is AMOT; the disease is head and neck cancer.