Mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase (HMGCS2) is a rate-limiting enzyme for ketogenesis that catalyzes the first enzymatic reaction in the ketogenic process, and HMGCS2 expression is associated with clinical prognosis and poor prognosis in patients with colorectal cancer and oral squamous cell carcinoma. Here, HMGCS2 is linked to oral cavity squamous cell carcinoma.