Objective To analyze the effect of trastuzumab combined with SOX regimen in advanced gastric cancer patients with positive human epidermal growth factor receptor 2 (HER-2) and the influence of serum tumor markers and immune function. Methods A total of 89 patients with advanced gastric cancer with HER-2 positive admitted to the First People's Hospital of Shangqiu City from August 2019 to July 2021 were selected as research objects and divided into conventional group and research group by lottery method. Forty-four patients in the conventional group received SOX regimen (oxaliplatin + Tizio) chemotherapy, and 45 patients in the study group were additionally given trastuzumab. After 4 courses of treatment, total response rate, serum tumor markers, immune function and adverse reactions were compared between the two groups. Result sThe total effective rate of the study group was 68.89%, which was higher than 47.73% of the conventional group (P<0.05). The serum levels of carbohydrate antigen 199 (CA199), carcinoembryonic antigen (CEA) and carbohydrate antigen 724 (CA724) in the study group were lower than those in the conventional group (P<0.05). The levels of CD8 ⁺, CD3 ⁺ and CD4 ⁺ in the study group were higher than those in the conventional group (P<0.05). The incidence of bone marrow suppression, gastrointestinal reaction, liver function injury and hand-foot syndrome were compared between the two groups (P>0.05). Conclusion Trastuzumab combined with SOX regimen is effective in the treatment of advanced gastric cancer patients with positive HER-2, which can effectively improve the treatment effect, reduce the level of serum tumor markers, inhibit the decline of immune function, and has high safety.