In conclusion, we demonstrated that the AST/ALT ratio is a prognostic factor of HNSCC. Among patients with stage IVA HNSCC, the subset with a high AST/ALT ratio had the worse prognosis. Therefore, they can be considered as candidates for intensified treatment. Moreover, the metabolic change that was observed as an increased AST/ALT ratio might be a substitute for a prognostic role of FDG-PET. Because of easy measurement and its potential utilities, further studies on this topic should be encouraged.