Background: With the development of endoscopic technology, the clinical detection rates of duodenal lesions have been significantly increased. Endoscopic submucosal dissection (ESD) has been increasingly applied to the minimally invasive treatment of duodenal space-occupying lesions and has similar therapeutic effects as surgery. However, postoperative complications such as perforation and bleeding easily occur after ESD, but there were few reports about it. We report a case, which we designed to evaluate the efficacy and safety of ESD treatment for stromal tumor in descending duodenum. Case presentation: A 64-year-old woman suffered from duodenal fistula and retroperitoneal abscess after ESD for stromal tumor in descending duodenum. The purse-string suture therapy of the wound was not very effective for the patient during the operation. Thus, the patient underwent a series of treatment measures successfully, such as endoscopic jejunum feeding tube placement, anti-infection, endoscopic closure of duodenal fistula, etc, and without evidence of perforation of duodenum. Follow-up was done for 6 months without recurrence. Conclusions: ESD is a efficient and promising strategy for treating of stromal tumor in descending duodenum, while the ESD of security needs to be further evaluated.