Objective: To investigate the surgical treatment strategies for patients with gastric mucosal lesions diagnosed as high-grade intraepithelial neoplasia (HGIN) by gastroscopic biopsy. Methods: The clinical data of 70 patients admitted in the Department of Gastrointestinal Surgery of Tongling People’s Hospital from January 2014 to September 2017 with initial diagnosis of HGIN made by gastroscopic biopsy and undergoing histopathological assessment of the whole lesion after radical resection and/or endoscopic treatment were retrospectively analyzed. Results: In the whole group of cases, the postoperative pathological examination confirmed the diagnosis of HGIN in 7 cases (10.0%), while it revealed low grade intraepithelial neoplasia or chronic inflammation in 3 cases (4.3%), diffuse large B cell lymphoma in 1 case (1.4%) and adenocarcinoma in 59 cases (84.3%). Univariate analysis showed that age (P=0.029), suspicious submucosal invasion by EUS (P<0.001), and perigastric lymph node enlargement (P=0.029) were significant risk factors for very low preoperative diagnosis. The team of the authors based on the clinical factors such as endoscopic diagnosis, imaging evaluation and serum CEA level, developed a decision tree method for surgical treatment option of gastric lesions diagnosed as HGIN by biopsy. Conclusion: Based on the development of endoscopic diagnosis and treatment technologies in recent years, the principle of individualized precise surgical treatment should be followed in patients with gastric mucosal lesions diagnosed as HGIN by biopsy, so as to avoid an over- or under-treatment.