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Jiangfan Yu,1 Rui Tang,2 Ke Ding3 1Department of Dermatology, Second Xiangya Hospital of Central South University, Changsha, 410011, People’s Republic of China; 2Department of Rheumatology and Immunology, Second Xiangya Hospital of Central South University, Changsha, 410011, People’s Republic of China; 3Department of Urology, Xiangya Hospital of Central South University, Changsha, 410008, People’s Republic of ChinaCorrespondence: Ke Ding, Department of Urology, Xiangya Hospital of Central South University, Changsha, 410008, People’s Republic of China, Email dingke@csu.edu.cnAbstract: Systemic sclerosis is a rare chronic autoimmune disease, which mainly manifests as immune disorders, vascular damage, and progressive fibrosis. The etiology of SSc is complex and involves multiple factors. Both genetic and environmental factors are involved in its pathogenesis. As one of the molecular mechanisms of environmental factors, epigenetic regulation plays an important role in the occurrence and development of systemic sclerosis, which involves DNA methylation, histone modification and non-coding RNA regulation. This review summarizes research advances in epigenetics, including exosomes, lncRNA, and mentions possible biomarkers and therapeutic targets among them.Keywords: systemic sclerosis, pathogenesis, epigenetics, biomarkers