AIM: The aim of this paper is to explore the expression of 6-methyladenine (6mA) DNA and to elucidate its gene regulation role in systemic lupus erythematosus (SLE). METHODS: Twenty SLE patients and 20 normal control healthy individuals (HCs) were included in this study. Genomic DNA was isolated from peripheral blood mononuclear cells and subsequently underwent 6mA-immunoprecipitation-sequencing (6mA-IP-Seq) after DNA quality control and 6mA precipitation. Bioinformation analysis was applied to the raw data comparing 6mA levels between SLE patients and HCs. RESULTS: We identified 5462 hypermethylation and 431 hypomethylation genes in PBMCs of individuals with SLE, which indicated that a high level of 6mA participates in the pathogenesis of SLE. Gene ontology analysis revealed that hypermethylation genes might regulate the inflammatory process, which has been well documented in the pathogenesis of SLE. CONCLUSION: 6mA may be involved in the initial development of SLE, which may lead to its potential use as an early diagnostic marker and therapeutic target.