To explore the effect of Mycophenolate mofetil combined with Glucocorticoid on renal function indicators such as serum creatinine (Scr), blood uric acid (BUA), blood urea nitrogen (BUN), 24-hour urine protein (PRO) quantification, as well as cellular and humoral immune function indicators in children with henoch-schonlein purpura nephritis, provide a basis for the treatment of this disease. Methods 42 cases children with henoch-schonlein purpura nephritis in Children's Hospital of Hebei Province from January 2020 to December 2022 were divided into the control group (21 cases) and the observation group (21 cases) by the random number table method. All the children were treated with symptomatic treatment, and children in the control group were treated with Prednisone and Cyclophosphamide, and children in the observation group were treated with Prednisone and Mycophenolate mofetil, the curative effects of children in the two groups were compared 6 months after treatment. The clinical efficacy of children, the renal function and immune function indicators before and 6 months after treatment, and the occurrence of adverse reactions during treatment between the two groups were compared. Results The total clinical effective rate of children in the observation group was higher than that in the control group; compared with before treatment, the levels of Scr, BUA, BUN, 24 h PRO quantification, immunoglobulin A (IgA), immunoglobulin G (IgG) and CD8+ percentage of children in the two groups decreased 6 months after treatment, and the observation group was lower than the control group; the CD3+ , CD4+ percentage, and CD4+ /CD8+ ratio of children in the two groups decreased 6 months after treatment, and the observation group was higher than the control group (all P<0.05); there was no significant difference in the total incidence of adverse reactions of children during the treatment between the two groups (P>0.05). Conclusion Mycophenolate mofetil combined with Glucocorticoid can improve the clinical efficacy of children with henoch-schonlein purpura nephritis, improve renal, inhibit the body's humoral immune response, and the safety is good.