OBJECTIVE： To discuss the effect of trastuzumab combined with chemotherapy on efficacy and serum tumor markers in patients with human epidermal growth factor receptor 2 （HER2） positive advanced gastric cancer. METHODS： 74 advanced gastric cancer patients in HER2 positive were randomly divided into observation group and control group， 37 cases in each group. Control group received cisplatin + capecitabine chemotherapy； based on it， observation group additionally received trastuzumab by intravenous infusion in the first day， 8 mg/kg. 21 d was a course， and it lasted for 6 months. The short-term efficacy， long-term efficacy， serum tumor marker contents and toxic and side effects were compared between 2 groups. RESULTS： The effective rate （56.76％ vs. 32.44％） and control rate （89.19％ vs. 65.86％） in observation group were significantly higher than control group， the differences were statistically significant （P＜0.05）； progression-free survival time and median survival time in observation group significantly longer than control group， the differences were statistically significant （P＜0.05）； contents of serum carcinoembryonic antigen， carbohydrate antigen  （CA）199， CA724 in observation group significantly lower than control group， the differences were statistically significant （P＜0.05）. And there were no significant differences in the incidences of nausea and vomiting， liver damage， bone marrow suppression and hand-foot syndrome in 2 groups （P＞0.05）. CONCLUSIONS： Trastuzumab combined with chemotherapy helps to reduce serum tumor markers content， and improve short-term efficacy， long-term efficacy of advanced gastric cancer patients with positive HER2.