Thrombotic microangiopathy (TMA) includes a series of life-threatening disorders. Systemic lupus erythematosus (SLE) is one of the most common acquired causes. To identify predictors of prognosis in patients with TMA secondary to SLE, we conducted a single-center historical study. From January 2013 to June 2016, of 2182 SLE hospitalized patients in the Ren Ji Hospital, a total of 21 consecutive patients with TMA secondary to SLE were identified. The 90-day short-term mortality was 33.3%. The kidney involvement (66.7%) was associated with poor prognosis, while the administration of rituximab (n = 13) was an independent protective factor according to logistic regression analysis. Compared to conventional treatment, i.e., plasma exchange, high-dose glucocorticoids, and intravenous immunoglobulin, the overall survival is significantly higher among patients receiving rituximab add-on (92.2 vs 33.3%, p = 0.0173); however, five out of seven patients with renal involvement in the rituximab group were eventually hemodialysis dependent. Our data indicated that add-on rituximab in the background of conventional therapy may improve the overall but not the renal survival in SLE-TMA patients.