VPA disrupted the self-renewal of HNSCC CSCs by downregulating the expression of stem cell markers, such as Oct4, Sox2, and CD44. Combining VPA with cisplatin further diminished HNSCC CSC chemoresistance, likely by suppressing ABCC2 and ABCC6 expression and enhancing caspase-mediated apoptosis. This evidence concerns the gene SOX2 and head and neck squamous cell carcinoma.