[Abstract] Objective To provide reliable evidence for guiding clinical practice, we conducted a comprehensive and objective evaluation of the safety and efficacy of mitoxantrone in treatment of multiple sclerosis. Methods Computer retrieval of Wanfang database, China academic journal full-text database (CNKI), VIP database, PubMed, the Cochrane Library was used, retrieval time was from build time of the database to December 2012. Randomized controlled trials of mitoxantrone treatment for multiple sclerosis were collected, and then used RevMan5.0 to conduct a meta-analysis. Results Finally 3 randomized controlled trials were included in the study, 281 patients including 171 examples of mitoxantrone treatment group, 110 cases of the placebo group. Meta-analysis showed: compared with placebo group, the recurrence rate of mitoxantrone treatment group was obviously lower (MD=1.02,95% CI:1.69~0.35,P=0.0027); EDSS score of mitoxantrone treatment group was obviously lower (MD=0.36,95% CI:0.70~ 0.02,P=0.036); the number of new or expanded damage confirmed by the magnetic resonance imaging (MRI) was no statistically significant difference between the two groups (MD=0.79, 95% CI:1.68~0.09,P=0.079). Adverse reactions of amenorrhea, nausea, vomiting, hair loss, the incidence of urinary tract infection were on the high side in mitoxantrone treatment group. However, the number of patients of discontinuation due to the adverse reactions was no statistically significant difference between the two groups (OR=2.72, 95% CI: 0.51~14.54, P= 0.24). Conclusion Curative effect of mitoxantrone is superior to placebo in the treatment of multiple sclerosis, serious adverse reactions were not found temporarily, and mitoxantrone treatment for multiple sclerosis may have certain advantages. However, the long-term curative effect and security still need large sample, multicenter randomized controlled trial to further confirm.