Systemic lupus erythematosus (SLE) is a typical autoimmune disease characterized by the production of autoantibodies and the damage of multiple organs. T lymphocytes play an important role in the autoimmune responses. Epigenetic factors have significant effects on T-cell functions by modulating its DNA methylation pattern. Gene-specific DNA hypomethylation happens in T cells in patients with active lupus. 5-azacytidine (5-azaC), and other demethylating agents like procainamide and hydralazine could induce lupus-like autoimmunity in vitro and in vivo. DNA hypomethylation in CD4+ T cell causes several gene activations and molecule overexpressions, and alters cellular function. Aberration DNA methylation in T cells might be responsible for idiopathic lupus and drug-induced lupus.