To investigate the efficacy and safety of tacrolimus(TAC)in treating pediatric refractory nephrotic syndrome(PRNS).Firstly,four self pre-and post-control observations of tacrolimus were implemented to verify the therapeutic effect of tacrolimus on PRNS.Secondly,three randomized controlled trials and one comparative cohort study was used to demonstrate the efficacy and safety of TAC comparing with other immunosuppressive therapies in treating PRNS.The included studies were of moderately high quality.Compared with pre-treatment,post-treatment of TAC significantly reduced urine protein/creatinine ratio(mean difference =-5.78,95%CI:-8.00 to-3.55,P < 0.00001).Compared with mycophenolate mofetil and cyclophosphamide,TAC achieved higher rates of complete remission(risk ratio = 1.79,95%CI: 1.11-2.90,P = 0.02 and risk ratio = 3.07,95%CI: 1.78-5.29,P < 0.0001,respectively).Compared with ciclosporin A,no significant difference in complete remission rate,however,TAC significantly reduce adverse events of nephrotoxicity and hypertrichosis(odds ratio = 0.25,95%CI: 0.08-0.74,P = 0.01 and odds ratio = 0.00,95%CI: 0.00-0.02,P < 0.00001,respectively).Overall,no obvious evidence of publication bias was found.TAC is considered to be a promising drug for treating PRNS.