The aim of this study was to assess the efficacy and safety of tacrolimus for the treatment of lupus nephritis (LN). A systematic review of clinical trials on tacrolimus in LN was conducted. Seven studies met the review inclusion criteria. Two studies were case-control studies, and five studies were open-label trials. One randomized controlled trial (RCT) found that tacrolimus significantly improved lupus nephritis disease activity index (LNDAI) as compared with a placebo, but no difference was observed between these two groups in terms of treatment-related adverse events. The other case-control study compared tacrolimus with standard protocols of oral cyclophosphamide or azathioprine for the treatment of membranous LN and found that efficacies were similar. All five open-label prospective studies concluded that tacrolimus is safe and effective as an induction and maintenance therapy for LN or for the treatment of LN with persistent proteinuria that failed to respond to prednisolone and immunosuppressants. In conclusion, this systematic review shows that tacrolimus may be effective as an induction and maintenance therapy for LN or as a treatment for LN with persistent proteinuria despite gold standard treatment. However, further RCTs are needed to compare tacrolimus with standard regimens for the treatment of LN.