Objective To analyze the effect of Trastuzumab combined with DS chemotherapy on serum tumor markers and functional status (KPS rating) of advanced gastric cancer patients with positive human epidermal growth factor receptor 2(HER-2). Methods 62 patients with HER-2 positive advanced gastric cancer from September 2016 to April 2018 were selected and divided into combined group (n=31) and DS group (n=31) according to different treatment Methods. DS group was treated with DS chemotherapy, while combined group was treated with Trastuzumab on the basis of DS group. The carbohydrate antigen 199 (CA199), carcinoembryonic antigen (CEA), gastric cancer antigen (CA724) and KPS scores before and after treatment were observed and compared between the two groups. Results KPS score of combined group was higher than DS group after treatment. After treatment, the levels of serum CA199, CEA and CA724 in the combined group were lower than those in the DS group, and the differences between the groups were statistically significant (P < 0.05). Conclusion The application of Trastuzumab combined with DS chemotherapy in HER-2 positive advanced gastric cancer patients can reduce serum CA724, CA199 and CEA levels and improve the quality of life.