Mechanistically, platyphyllenone exerts its anti-cancer effects by reducing the phosphorylation of p38, upregulating the expression of E-cadherin, and downregulating the expression of cathepsin L. Taken together, the study identifies platyphyllenone as a potential anti-metastatic agent that may be used clinically to manage highly metastatic human oral squamous cell carcinomas. Here, CDH1 is linked to oral cavity squamous cell carcinoma.