The aim of the present study was to investigate the clinical outcome of mycophenolate mofetil in pediatric refractory gastrointestinal (GI) Henoch-Schönlein purpura (HSP). Most of the HSP patients with GI symptoms may benefit from early introduction of glucocorticoid; however, a number of patients still do not achieve remission following the administration of steroids. Therefore, the present study was to investigate the clinical features and the clinical outcome of mycophenolate mofetil in refractory GI HSP. A total of 110 HSP patients with a median onset age of 6.3 years were included. Sixty-one (55.5%) exhibited GI involvement, and 18 (18/61, 29.5%) presented with refractory GI involvement, with a median onset age of 6.3 years. Intractable abdominal pain, GI hemorrhage, intussusception, and chronic ulcers were common presentations of GI involvement. Of those refractory ones, Arthralgia was observed in 9 cases and renal involvement was observed in 13 cases. Glucocorticoids were administered in all 18 patients, but remission was not achieved. However, complete remission of abdominal pain was achieved in all patients within a median time of 3 days (1-14 days) after mycophenolate mofetil therapy. The infection rate of Epstein-Barr virus and cytomegalovirus in the refractory group was significantly higher compared with that in non-refractory group.Conclusion: GI symptoms in HSP patients with refractory GI involvement were more severe compared with non-refractory cases. Epstein-Barr virus and cytomegalovirus infection may be risk factors for refractory GI HSP. The efficacy of mycophenolate mofetil treatment was evident in these patients. What is Known: • Abdominal pain, gastrointestinal hemorrhage, intussusceptions, and intestinal perforation were the main presentations of gastrointestinal involvement in Henoch-Schönlein purpura. What is New: • Epstein-Barr virus and Cytomegalovirus infection may be the high risk factor of refractory GI. Refractory gastrointestinal Henoch-Schönlein purpura was associated with renal involvement. • Mycophenolate mofetil treatment was effective for refractory gastrointestinal Henoch-Schönlein purpura.