This study mainly explored the influence of tacrolimus in association with mycophenolate mofetil (MMF, CellCept) in treating steroid-resistant nephrotic syndrome (SRNS) children. A total of 124 SRNS children were chosen and separated into observation group and control group. The control group received basic treatment and tacrolimus treatment. In contrast, the observation group received MMF in addition to basic and tacrolimus treatments. The results showed that the observation group presented higher total effective rate, better improvements of 24 h urinary protein quantification, than the control group. Albumin and cholesterol levels, lower fibrinogen level, lower blood urea nitrogen, serum creatinine, along with cystatin C levels, better improvements of interferon γ, interleukin-2 and interleukin -13 levels, and lower total occurrence of adverse reactions. We conclude that Tacrolimus combined with MMF can effectively reduce inflammation along with improve the renal function of SRNS children.