Abstract: Objective To observe the clinical effect of tacrolimus combined with prednisone in the treatment of patients with refractory idiopathic membranous nephropathy. Methods One hundred patients with refractory idiopathic membranous nephropathy were randomly divided into two groups, with 50 cases in each group. The control group was treated with cyclophosphamide and prednisone, while the observation group was treated with tacrolimus and prednisone. Both groups were treated for 12 months. The clinical efficacy, serum albumin, 24 h urine protein quantification and occurrence of adverse reactions were compared between two groups. Results The total remission rate of the observation group was significantly higher than that of the control group(P<0.05). After 1 month, 3, 6 and 12 months of treatment, the serum albumin level of the observation group was significantly higher than that of the control group, and the 24 h urinary protein quantification was significantly lower than that of the control group(P<0.05). No serious adverse reactions occurred in both groups. Conclusion Tacrolimus combined with prednisone is effective in the treatment of patients with refractory idiopathic membranous nephropathy, which can increase the level of serum albumin and reduce 24 h urine protein quantification.