Her2-positive gastric cancer is a unique subtype of disease, requiring different diagnosis and treatment strategies and methods. Neoplasms are significantly correlated with the occurrence, invasion and metastasis of tumors. The purpose of this study was to explore the correlation between HER2 amplification and tumor interstitial angiogenesis in patients with gastric cancer. The data of 1121 patients with gastric cancer were retrospectively analyzed, and the amplification of HER2 was detected by immunohistochemistry (IHC) and FISH. CD34 IHC was used to label MVD. We analyzed the factors affecting HER2 amplification, the difference in MVD under different HER2 states, the factors related to 5-year survival rate of patients, and predicted the independent factors affecting 5-year survival rate of gastric cancer patients. We found 115 cases with HER2 positive rate of 10.26 %. HER2 amplification was more likely in gastric cancer patients with more than 5.2 cm tumor diameter, Lauren intestinal type, tubular adenocarcinoma, and the depth of infiltration at stage T2, (P < 0.05). Gender, age, tumor location, number of lymph node metastasis, distant metastasis, clinical stage, nerve invasion and vascular tumor thrombi were not the factors affecting HER2 amplification of gastric cancer (P > 0.05). MVD count of HER2-positive gastric cancer was significantly higher than that of HER2-negative gastric cancer, (P < 0.05). The 5-year overall survival rate of 1121 patients with gastric cancer was 51.92 %. HER2 amplification, high MVD count, large tumor size, tubular adenocarcinoma, Lauren intestinal type, deep tumor infiltration, numerous lymph node metastases and late clinical stage are all associated with low 5-year survival rate, indicating poor prognosis in gastric cancer patients, (P < 0.05). The 5-year survival rate of gastric cancer patients was not correlated with gender, age, tumor location, distant metastasis, nerve invasion and vascular cancer plug, (P > 0.05). Multivariate analysis showed that Lauren classification, Infiltrating depth, Nodal status, Clinical stage, HER2 expression, MVD count were independent factors affecting the prognosis of gastric cancer patients, (P < 0.05). HER2 overexpression was not only closely related to gastric cancer neovascularization, but also an independent predictor of prognosis of gastric cancer. In clinical treatment, anti-HER2 targeted therapy and anti-angiogenesis drugs can be adopted to achieve effective treatment. Copyright © 2020 Elsevier GmbH. All rights reserved.