Abstract: OBJECTIVE To investigate the chemopreventive effect of quercetin on oral squamous cell carcinoma (OSCC) by regulating NF-κB signaling pathway. METHODS Golden hamster buccal pouch carcinoma model was established by DMBA Induction. The model was divided into 6 groups: blank control group， quercetin administration group， DMBA model group， low dose prevention group， medium dose prevention group， high dose prevention group， qPCR and Western Blot to detect NF-κB. The expressions of NF-κB-p50， NF-κB-p65， IκBα， p- IκBα and IKKβ were detected， and the chemical components of quercetin were docked with IKK beta kinase. Computer-aided virtual docking method was used to simulate the docking of quercetin with IKK beta kinase molecule. RESULTS Western blot analysis showed that the expression levels of NF-κB-p50， NF-κB-p65， p-IκBα and IKKβ in medium dose prevention group and high dose prevention group were significantly lower than those in DMBA model group， but the expression levels of IκBα were significantly higher than those in DMBA model group. qPCR results showed that the expression levels of NF-κB-p50 mRNA and NF-κB-p65 mRNA in high dose prevention group were significantly lower than those in DMBA model group. Molecular simulation docking results showed that quercetin docked with IKK beta kinase region in the same active chamber through hydrogen and PI bonds. CONCLUSION Quercetin may play a chemopreventive role in oral squamous cell carcinoma by targeting the NF-κB signaling pathway.