Poor prognosis is associated with oral squamous cell carcinoma (OSCC), an aggressive form of malignant tumor.1 Developing effective targeted therapies against OSCC is anticipated to have significant clinical implications. Fisetin (3, 3′, 4′, 7-tetrahydroxyflavone), a natural flavonoid, the most common phytochemical found in a variety of fruits and vegetables, may bring several therapeutic potential benefits to people.2 Investigating the pharmacological impact of natural flavonoid fisetin on the management of OSCC was the aim of the current investigation. By focusing on the tumor-associated antigen MUC1 (mucin 1), fisetin prevents OSCC cells from transforming malignant. This study aims to provide new diagnostic indicators and therapeutic targets for the diagnosis and treatment of OSCC by exploring the role and mechanism of fisetin in OSCC.