Abstract: Objective To investigate the curative effect and safety of tacrolimus combined with methylprednisolone analysis in the treatment of lupus nephritis. Methods Total 64 cases of lupus nephritis in our hospital between November, 2012 and October, 2015 were enrolled and divided into study group and control group, 32 cases in each group. The study group received tacrolimus combined with methylprednisolone, while the control group received cyclophosphamide and methylprednisolone treatment. The remission rate, incidence of adverse reactions was compared between the two groups.The levels of 24-hour urine protein, serum creatinine (Scr), C3, serum albumin (ALB), and systemic lupus erythematosus disease activity index (SLEDAI) score were recorded before and after treatment in both groups. Results The effect in the study group was significantly better than that in the control group, the difference was statistically significant (Z=2. 223, P < 0. 05). After the treatment, the levels of 24-hour urine protein, Scr and SLEDAI decreased, and levels of C3 and ALB significantly increased in both groups, the difference was statistically significant (P < 0. 05). The levels of 24-hour urine protein and SLEDAI in the study group were lower than those in the control group, but the levels of Scr, C3 and ALB were significantly higher than those in the control group, the difference was statistically significant (t=4. 538, 3. 896, 2. 287, 5. 492, 6. 342, P < 0. 05). The incidence rate of adverse reaction in the study group (15. 62%) was significantly lower than that (40. 62%) of the control group, the difference was statistically significant (χ²=4. 947, P < 0. 05). Conclusion Tacrolimus combined with methylprednisolone has definite efficacy for lupus nephritis, which can significantly reduce the urinary protein level, effectively control of the disease, and with a high safety.