Objective To evaluate the preliminary efficacy and safety of XELOX combined with trastuzumab in the transformation therapy of human epidermal growth factor receptor 2 (HER2) positive elderly patients with advanced gastric cancer. Methods The clinical and surgical data of 21 patients with HER2 positive elderly patients with advanced gastric cancer who were treated with XELOX combined with trastuzumab in our Hospital from February 2019 to February 2021 were retrospectively analyzed, and the remission of patients after conversion therapy and the relevant indicators during and after surgery were observed. Results After the conversion therapy, there were 2 cases (9.5%) of complete remission, 13 cases (61.9%) of partial remission, and 6 cases (28.6%) of stable disease, the remission rate of the conversion therapy was 71.4% (15/21). After conversion treatment, 21 patients underwent laparoscopic exploration, of which 20 patients (95.2%) underwent R0 resection, simple exploration 1 case. In all 21 cases, the operative time was 124–185 min, with a median of 152 min. The intraoperative blood loss was 100–210 mL, with a median of 120 mL. The number of lymph nodes cleared was 12–54, with a median of 32. The duration of indwelling gastrointestinal decompression was 51–134 h, with a median of 102 h. The recovery time of gastrointestinal function was 70–98 h, with a median of 78 h. The drainage time in the abdominal operation area was 4–9 days, with a median of 6 days. Postoperative hospital stay was 7–13 days, with a median of 8 days. There were 2 cases of Grade IIIA complications (1 case of incomplete intestinal obstruction and 1 case of pulmonary infection) and 2 cases of Grade II complications (1 case of incision fat liquefaction and 1 case of jugular catheter infection) after operation. All patients were followed up for 3–36 months, with a median of 16.8 months. The median progression-free survival time was 12.4 months and the median overall survival time was 20.5 months. Conclusion For HER2 positive elderly patients with advanced gastric cancer, XELOX combined with trastuzumab transformation therapy is effective and safe.