Objective: To explore the influence of intervention regimen based on interactive intervention model on the efficacy of children with Henoch-Schonlein purpura nephritis (HSPN) and disease uncertainty of family members. Methods: 132 children with HSPN were divided into two groups according to different intervention methods. The study group (n=66) implemented interactive intervention model, the control group (n=66) received routine nursing care, and the intervention time was 3 months. The efficacy, symptom regression time, renal function indicators (Urine red blood cell count, urine microalbumin, 24-hour urine protein quantification), and disease awareness rate, satisfaction and disease uncertainty (MUIS-FM) scores of family members were compared between both groups. Results: The effective rate of nursing care in the study group after intervention was higher than that in the control group (P<0.05). The regression times of various symptoms were shorter in the study group than those in the control group (P<0.05). After intervention, urine red blood cell count, urine microalbumin, and 24-hour urine protein quantification in the study group were lower compared with those in the control group (P <0.05). The disease awareness rate and nursing care satisfaction of family members in the study group were higher compared to the control group (P<0.05). The scores of dimensions of MUIS-FM were lower in the study group compared with those in the control group (P<0.05). Conclusion: Nursing based on interactive intervention model for HSPN children can enhance the therapeutic effect, promote the symptom regression, improve the renal function, enhance the disease awareness rate and satisfaction of family members, and reduce the disease uncertainty.