Abstract： Objective To assess the efficacy and safety of mycophenolate mofetil(MMF)combined with Leflunomide(LEF)in the multi-target induction therapy for lupus nephritis.Methods Between May 2010 and June 2013,a total of 70 cases of kidney biopsy proved lupus nephritis at Huizhou Central People's Hospital were recruited in this study.Of these patients,the classification of lupus nephritis included typeⅢ,Ⅳ,Ⅲ+Ⅴ,andⅣ+Ⅴ,the score of chronic index(CI)was below 4,and the patient age was below 18 years old.The patients were randomly assigned to either multi-target induction therapy group[MMF(1.0 g/d)and LEF(10 mg/d)for 6 months]or intravenous cyclophosphamide pulse therapy group(as the control group) [IV-CYC(0.5-1.0)g/m2,one times a month,6 months],with 35 patients in each group,The two groups received methylprednisolone(MP)pulse therapy at an initial dose of 500 mg for 3 d,followed by 4-week maintenance with oral prednisone(0.5 mg·kg-1·d-1)before tapering.The renal complete remission(CR)or partial remission(PR),reduction in SLEDAI scores,and anti-ds-DNA antibodies were evaluated.Incidence of major adverse reactions,such as gastrointestinal symptoms,upper airway infection,neutropenia,menstrual disorders and shingles,was noted and compared between the two groups.Results 62 patients were included in the final analysis,including 33 from the multi-target induction therapy group,and 29 from the control group.The overall rate of CR or PR did not differ significantly between the two group(P>0.05).However,the multi-target induction therapy group showed higher rates of CR in patients with classⅣ+Ⅴ(44.4%vs 12.5%,P=0.026),and classⅢ+Ⅴ(60%vs 20%,P<0.05)lupus nephritis,compared with the control group.Moreover,the CR or PR rate of classⅣ+Ⅴlupus nephritis in multi-target therapy group was notably much higher than that in control group(77.8%vs 50%,P=0.018).The SLEDAI scores and ds-DNA levels were statistically comparable between the two groups.The gastrointestinal symptoms and upper airway infections in the multi-target therapy group were less frequent than those in the control group (6.1% vs 48.3%,P=0.032;9.1% vs 24.1%,P=0.041).Neutropenia occurred in 2 patients each of the either group.There were also two cases of menstrual disorder(6.9%)and two of shingles(6.9%)in the control group.Conclusion Multi-target therapy with MMF and LEF offers a better efficacy and safety than conventional treatment options for lupus nephritis.