Hereby we discovered that periodontitis-level sodium butyrate treatment-induced ferroptosis in PDLFs, and the onset of ferroptosis is closely correlated with activation of NCOA4-mediated ferritinophagy; moreover, the p38/hypoxia inducible factor-1α (HIF-1α) pathway activation as well as bromodomain-containing protein (BRD) 4 and cyclin-dependent kinase 9 (CDK9) coordination regulated onset of ferritinophagy and ferroptosis. This evidence concerns the gene HIF1A and periodontitis.