Since myeloid-derived suppressor cells (MDSCs) were found suppressing immune responses in cancer and other pathological conditions, subsequent researchers have pinned their hopes on the suppressive function against immune damage in autoimmune diseases. However, recent studies have found key distinctions of MDSC immune effects in cancer and autoimmunity. These include not only suppression and immune tolerance, but MDSCs also possess pro-inflammatory effects and exacerbate immune disorders during autoimmunity, while promoting T cell proliferation, inducing Th17 cell differentiation, releasing pro-inflammatory cytokines, and causing direct tissue damage. Additionally, MDSCs could interact with surrounding cells to directly cause tissue damage or repair, sometimes even as an inflammatory indicator in line with disease severity. These diverse manifestations could be partially attributed to the heterogeneity of MDSCs, but not all. The different disease types, disease states, and cytokine profiles alter the diverse phenotypes and functions of MDSCs, thus leading to the impairment or obversion of MDSC suppression. In this review, we summarize the functions of MDSCs in several autoimmune diseases and attempt to elucidate the mechanisms behind their actions.© 2023. The Author(s).