Objective To investigate the safety and efficacy of submucosal tunnel docking endoscopic resection (SDER) for the treatment of giant submucosal tumors in the cardia. Methods A retrospective analysis was performed on data of patients with giant submucosal tumors in the cardia who were treated with SDER at the endoscopy center of Zhongshan Hospital, Fudan University and Xuhui District Central Hospital from January 2021 to January 2022. The surgical records, postoperative pathology, complications, hospitalization, and follow-up were analyzed. Results A total of 6 patients were included. The mean long diameter of the lesions was 4.0 cm, all of which were located in the cardia. All patients successfully underwent SDER treatment with a surgical time of 23-42 min. Postoperative pathology revealed that 4 cases were leiomyomas and 2 cases were gastrointestinal stromal tumors. All lesions were completely resected. The postoperative hospital stay was 3-5 d, and no serious complications occurred after surgery. All patients recovered on follow-up gastroscopy at 3 and 6 months postoperatively. Conclusion The preliminary conclusion is that SDER for the treatment of giant submucosal tumors in the cardia is safe, effective.