Background and Aims Brunner's gland hamartoma (BGH) is a rare type of duodenal benign tumor. It is difficult to diagnose before operation and often easily to be missed or misdiagnosed because of atypical clinical manifestations and lack of specificity. The diagnosis mainly depends on postoperative pathology. The cases of giant BGH are rare. This paper reports the diagnosis and treatment of a case of giant BGH with associated chronic anemia, and reviews the characteristics of this disease in combination with the previous literature, so as to provide experience for clinical management of this condition.Methods The clinical data of a patient with BGH admitted to the Department of Hepatobiliary Surgery of Xianyang Central Hospital Affiliated to Xi'an Jiaotong University were analyzed retrospectively in combination with a review of the previous literature.Results The patient was a 49-year-old female, and was admitted to the Department of Hepatobiliary Surgery of Xianyang Central Hospital Affiliated to Xi'an Jiaotong University because of abdominal pain accompanied by nausea and vomiting. The patient had a history of chronic anemia, regular menstruation, and occasional black stool. On admission, the B-ultrasound examination of the upper abdomen showed the mass of the duodenum overlapped by the head of the pancreas; CT examination of the upper abdomen showed diffuse thickening of the intestinal wall in the descending and horizontal parts of the duodenum, with unclear structure; MRI+MRCP examination of the upper abdomen showed that the descending and horizontal parts of the duodenum and the adjacent jejunum were indistinct, the intestinal tube was obviously distended and twisted, the intestinal wall was indistinct, with obvious intestinal wall edema and presence of concentric circles change. Duodenal space occupying was considered in gastroscopy, and biopsy under endoscopy suggested that it was consistent with the ectopic gastric mucosa. The upper gastrointestinal angiography showed a nearly round filling defect at the junction of the descending and horizontal segments of the duodenum, considered to be a benign occupying lesion. Finally, the obstruction caused by the duodenal space-occupying lesion was considered, and pancreaticoduodenectomy was performed after exploratory laparotomy. The final diagnosis was BGH and immunohistochemical staining for MUC5AC positive after the resected specimen was sent to pathological examination. The patient recovered uneventfully after surgery and was discharged from the hospital. After the operation, the blood routine was monitored, and the red blood cells and hemoglobin gradually returned to normal. The patients were followed up for 12 months. The patients were generally in good condition without complaints of discomfort. All indexes were normal in the reexamination, and the follow-up was continued.Conclusion Giant BGH with associated chronic anemia is rare in clinical practice. Preoperative imaging examination is often difficult to provide valuable information. Biopsy under gastroscope is helpful for diagnosis, but the positive rate is low. The final diagnosis depends on histopathological examination of the surgical specimens. Surgical resection is an effective means to treat the disease when the lesion is large.