Abstract: Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease. Although the prognosis of SLE patients has greatly improved in recent years, the mortality of severe lupus remains high. The manifestations of severe lupus fall into complex types, and evidencebased treatments are still lacking. Besides, the inappropriate use of glucocorticoid and immunosuppressive drugs may increase the risk of infection and other complications, resulting in disability and even death. In this review, we discussed the strategy of immunosuppressive therapy for different types of severe lupus, including neuropsychiatric lupus, lupus nephritis, cardiopulmonary involvement, gastrointestinal diseases and thrombocytopenia, so as to provide some reference for rational drug use in clinical practice.