We identified Follistatin (FST), a secreted glycoprotein and inhibitor of transforming growth factor TGF-β/Activin signaling pathways, as a p63 target in the epithelial component of the tumor microenvironment (TME) that might play a role in directing stemness and metastasis in HNSCC. Here, TGFB1 is linked to head and neck squamous cell carcinoma.