Abstract: Objective To compare the clinical efficacy of tacrolimus (FK506) and mycophenolate mofetil (MMF) combined with steroid respectively in the treatment of steroid dependent/frequent relapsing nephrotic syndrome (SDNS/FRNS) in children. Methods Forty-nine cases of Children with SDFN/SDNS from January, 2009 to July, 2015 were recruited, 21 cases in tacrolimus group, 28 cases in mycophenolate mofetil group, and the 28 cases were divided to MMFlow-concentration group[MPA-AUC < 30 μg/(ml·h)]and MMF-high-concentration group[MPA-AUC ≥ 30 μg/(ml·h)]according to the area under the curve of mycophenolic acid (MPA-AUC). The therapeutic effect of the groups were compared. Results (1) Steroid dosage:The steroid dose was reduced more significantly at 6-month follow-up (P <0. 01). The MMF-high-concentration group's was reduced the most, and it had significant difference compared with MMFlow-concentration group (P < 0. 05). No significant difference among the groups hormone dosage at 12-month follow-up (P > 0. 05). (2) Relapse episodes:The number of relapse episodes was reduced more significantly at 6-month follow-up (P < 0. 05) except MMF-low-concentration group. MMF-low-concentration group had the most number of relapse episodes during 6-month follow-up, and the result was significantly compared with MMF-high-concentration group (P < 0. 05). No significant difference occured in the relapse episodes of the groups at 12-month follow-up (P > 0. 05). Conclusion There is no significant difference in the clinical efficacy between FK506 and MMF combined with steroid respectively in the treatment of children with SDNS/FRNS. After 6 months of treatment, MMF-high-concentration can obtain a satisfactory therapeutic effect. For the children receiving low concentration MMF, the clinical effect can be similar with other patients if the disease did not frequently relapse in one year.