We uncover several interesting aspects of FST biology and function in HNSCC: first, we identified FST as super enhancer-associated gene in HNSCC whose expression is consistently downregulated in the absence of p63; second, we demonstrated that FST intrinsically mediates HNSCC cell clonogenicity and migration, presumably by neutralizing TGF-β/activin signaling. Here, TP63 is linked to head and neck squamous cell carcinoma.