Abstract: Long non-coding RNA (lncRNA) has a wide range of biological functions in epigenetic, cell cycle, cell differentiation and other life activities, and that affect the development and differentiation of immune cells and the maintenance of homeostasis in the immune system. CD4⁺ T cell subsets are heterogeneous cells with different functions, including promoting the proliferation and differentiation of T cells, B cells and other immune cells, and coordinating related functions between immune cells. Autoimmune disease (AID) is a chronic inflammatory disease caused by an autoantigen immune reaction. lncRNA and CD4⁺ T cell subsets are involved in the occurrence and progression of the disease. This article reviews the relationship between lncRNA and the differentiation of AID CD4⁺ T cell subsets.