Systemic lupus erythematosus (SLE) is an autoimmune disease that is characterized by multi-organ involvement leading to significant morbidity and mortality in predominantly young women. The underlying pathogenesis involves the emergence of autoreactive T and B lymphocytes, production of autoantibodies, formation and deposition of immune complexes in various tissues leading to inflammation and organ damage. Recently, growing evidence suggests that the functions of hematopoietic stem cells (HSCs) and mesenchymal stem cells (MSCs) are disrupted in SLE pathology. And HSC or MSC transplantation (HSCT/MSCT) can offer an effective and safe therapy for the severe SLE patients, resulting in disease clinical remission and improvement of organ dysfunction. In this article, we provide a brief overview of current research of autologous or allogeneic HSCT/MSCT in SLE and describe our current understanding of the mechanisms by which it plays a part in treating SLE, for better understanding of the pathogenesis, diagnosis and treatment for SLE.