AZGP1 was primarily colocalised with macrophages, by promoting M1 polarisation and pyroptosis through the NLR family pyrin domain containing 3 (NLRP3)/caspase‐1 pathway in periodontitis tissues, thus blocking the NLRP3/caspase‐1 pathway with NLRP3 or caspase‐1 inhibitor reversed macrophage M1 polarisation and pyroptosis induced by AZGP1 overexpression. This evidence concerns the gene NLRP3 and periodontitis.