Background To explore the changes of inflammatory and oxidative stress responses in Henoch-Schonlein purpura (HSP) children, and further analyzed the therapeutic effects and mechanisms of hemoperfusion (HP) on HSP with severe gastrointestinal (GI) involvement. Methods There were 200 children with HSP were divided into three groups according to their clinical manifestations: 60 in HSP without GI and renal involvement group, 60 in HSP with GI involvement group, and 80 in HSPN group. The HSP with GI involvement group was subdivided into conventional treatment (n = 30) and HP (n = 30) groups. Thirty children who visited the department of children healthcare for healthy physical examinations from January to December 2017 were set as healthy control group. The IL-6 and TNF-alpha levels were detected by chemoluminescence method. The MDA, SOD and T-AOC levels were determined by thiobarbituric acid colorimetric method, hydroxylamine method and chemical colorimetry. Results Compared with healthy group, IL-6, TNF-alpha and MDA levels in HSP were increased in each group, while SOD and T-AOC were decreased (P = 0.000). IL-6, TNF-alpha and MDA levels in the HSPN group were the highest, SOD and T-AOC levels were the lowest (P = 0.000). Compared with those before treatment, IL-6, TNF-alpha and MDA levels in the conventional and HP groups were decreased and SOD and T-AOC levels were increased (P = 0.000). The changes in HP group were more significant than those in conventional group (P < 0.047). Compared with conventional group, glucocorticoid dosage and the occurrence rate of hematuria and/or proteinuria within 3 months were lower in HP group. (P = 0.000, 0.004). Conclusions Inflammatory and oxidative stress may be involved in the acute phase of HSP children. The intensity of inflammatory and oxidative stress responses were related to the degree of renal involvement. HP can reduce glucocorticoid dosage and the rate of renal involvement in children with severe HSP with GI involvement. The mechanism may be related to the fact that HP can effectively remove IL-6, TNF-alpha, MDA in HSP children.