We had successfully constructed the model of periodontitis and identified that the periodontitis-related bacteria (P. gingivalis and F. nucleatum) could promote oral tumor growth and proliferation by initiating the overexpressed NLRP3 and activating upstream signal molecules of ATR-CHK1, which was innovative in the analytical elucidation of the possible linkages and regulatory mechanisms of periodontal bacterial infection–periodontitis–OSCC. This evidence concerns the gene NLRP3 and periodontitis.