Objective: To evaluate the safety and efficacy of tacrolimus combined with glucocorticoids in the treatment of lupus nephritis. Methods: A total of 80 patients with lupus nephritis were admitted to the Affiliated Hospital of Hebei University and the First Hospital of Baoding from February 2017 to January 2019 randomly divided into two groups: the experimental group and the control group, with 40 cases in each group. Patients in the experimental group were treated with tacrolimus combined with glucocorticoids, while patients in the control group were treated with cyclophosphamide combined with glucocorticoids for one year. Clinical efficacy and adverse drug reactions were evaluated for all patients after treatment. The changes of CRP, IL-6, 24h urinary protein, serum albumin, serum creatinine, urea nitrogen and other indicators after treatment, as well as the differences in the erythrocyte sedimentation rate (ESR), complement C3, C4, anti-dsDNA antibody positive rate and SLEDAI score and other indicators were also evaluated. Results: The total efficacy of the experimental group was 92.5%, which was significantly better than the 75% of the control group (p=0.03); The incidence of adverse reactions was 20% in the experimental group and 42.5% in the control group, with a statistically significant difference (p=0.03). After treatment, the levels of CRP, IL-6 and other inflammatory factors in the experimental group were lower than those in the control group, with a statistical significance (p<0.05); The indicators of the experimental group such as 24h urine protein quantification, serum albumin, blood creatinine, and urea nitrogen were improved compared with the control group, with statistically highly significant differences (p<0.001). In addition, ESR, antiDSDNA antibody positive rate and SLEDAI score were decreased compared with the control group, while complement C3 and C4 levels were significantly increased (p<0.05). Conclusion: Tacrolimus combined with glucocorticoids is a safe and effective treatment regimen for patients with lupus nephritis, boasting a variety of benefits, such as significant efficacy and fewer adverse reactions. With such a regimen, the level of inflammatory factors can be significantly reduced, renal function indicators can be ameliorated, the ESR, complement C3, C4, anti-dsDNA antibody positive rate and SLEDAI score of the patients can be significantly improved.