Oral squamous cell carcinoma (OSCC) is one of the main causes of death in oral diseases. With the development of nanotechnology, great progress has been made in the diagnosis and treatment of tumors in nanomedicine. Being able to carry drugs, nucleic acids, contrast agents, and so on, nano-medical technology can effectively reduce the toxicity of nano-carried materials while playing a drug role. Nano-drug delivery system can help diagnosis and treatment of OSCC. In the chemotherapy of OSCC, nano-drug delivery system can significantly increase the anti-tumor activity of drugs in drug-resistant strains resistant to chemotherapy and can achieve good curative effect. We summarized the research progress of nano-drug delivery system in OSCC by reviewing relevant literature, so as to provide some reference for relevant clinicians.