Objective:To study the safety and efficacy of hiatal hernia-endoscopic submucosal dissection (HH-ESD) for the treatment of giant hiatal hernia (>3 cm in length) complicated with refractory gastroesophageal reflux disease (GERD).Methods:Patients with giant hiatal hernia complicated with refractory GERD who voluntarily received HH-ESD at the Digestive Endoscopy Center of the Affiliated People's Hospital of Inner Mongolia Medical University from April 2018 to March 2020 were included in the clinical study. The completion of HH-ESD and the occurrence of complications were observed, and the changes of indicators before and after the treatment were observed, including gastroesophageal reflux disease-health related quality of life (GERD-HRQL) score, gastroesophageal reflux disease questionnaire (GERD-Q) score, endoscopy results, 24 h esophageal pH monitoring results, esophageal high-resolution manometry results and proton pump inhibitor (PPI) usage.Results:Data of 10 patients were collected during the study, with a medical history of 2-10 years. All patients successfully underwent HH-ESD treatment. No adverse events such as perforation and massive bleeding occurred during the operation, and the hospital stay was 6-12 days. Dysphagia occurred in 3 cases after the operation, which was relieved spontaneously within 3 or 6 months. The preoperative GERD-HRQL scores ranged from 19 to 29, which were reduced to 0-14 and 0-8 at 3 and 12 months after the operation, respectively. The preoperative GERD-Q score was 9-17, and the scores at 3 and 12 months after the operation were all 6-9, which were significantly lower than those before. Gastroscopy showed that esophagitis was improved in all patients, hernia sac was reduced, and Hill grade was reduced compared with that before. The preoperative DeMeester score was 30.3-247.1, and the postoperative 12-month score was 0.2-29.9, which was significantly lower than that before. The long diameter of hiatal hernia was 3.0-6.0 cm before the operation and 0-5.0 cm at 12 months after, which was smaller than that before. At 12 months of the follow-up, 7 patients had stopped PPI, and the remaining 3 had changed to intermittent oral PPI.Conclusion:Preliminary results show that HH-ESD is safe and effective for the treatment of giant hiatal hernia complicated with refractory GERD.