Systemic lupus erythematosus (SLE) is a chronic autoimmune disease, in which aberrant immune cells and proinflammatory mediators act as key players in the pathogenesis of the disease. Telitacicept (RC-18) is a novel, recombinant fusion protein, consisting of transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI) and the Fc portion of human immunoglobulin G (IgG) (TACI-Fc). It was designed to inhibit the activity of two target cytokines, the B-cell lymphocyte stimulator (BLyS, also known as the B-cell activation factor [BAFF]) and a proliferation-inducing ligand (APRIL), both of which are involved in B cell-mediated autoimmune diseases. In Chinese patients with moderate to severe SLE, subcutaneous telitacicept (80, 160 and 240 mg) in combination with standard therapy was associated with clinical benefit and appeared to be well tolerated. On March 9, 2021, the Chinese National Medical Products Administration (NMPA) granted telitacicept conditional marketing approval for the treatment of adult patients with active, autoantibody-positive SLE. Additionally, on April 15, 2020, the U.S. Food and Drug Administration (FDA) granted fast track designation to telitacicept for the treatment of SLE. Here, we provide a comprehensive review of the preclinical and clinical activity of telitacicept in SLE.