A biomarker is defined as a biological molecule found in the blood, other body fluids, or tissues that is a sign of normal or abnormal processes or a condition or disease. In cancer research, biomarkers are classified as diagnostic, prognostic, or predictive. The identification and application of biomarkers in clinical practice are important for evaluating their usefulness for clinical diagnosis, treatment and prognostic warning and for determining the biological effects of anti-cancer drugs, and they are currently one of the hottest topics in oncological translational research. Currently, translational research on biomarkers mostly focus on oncological diagnosis and molecular typing, targeted therapy, treatment protocol selection and optimization, prognostic prediction, etc. Here, we review the progress of translational research on treatments based on biomarkers in oral squamous cell carcinoma as well as the clinical application of inhibitors targeting EGFR, PD1, PI3K, WEE1, the Wnt/β-catenin pathway, the SHH pathway, and the ERK pathway. The prospect of research strategies for personalized treatments based on biomarkers in oral squamous cell carcinoma is also discussed.