Abstract: Objective To investigate the efficacy of sintilimab combined with oxaliplatin plus capecitabine chemotherapy in patients with advanced gastric cancer and its effects on tumor markers and immune function. Methods A total of 92 patients with advanced gastric cancer admitted to Fuyang Hospital Affiliated to Anhui Medical University from January 2022 to September 2024 were selected and randomly assigned to an observation group (n = 46) or a control group (n = 46). The control group received oxaliplatin plus capecitabine chemotherapy, while the observation group received sintilimab combined with oxaliplatin plus capecitabine chemotherapy. The clinical efficacy after 2 cycles was compared between the two groups. Changes in tumor marker levels, immune function, and quality of life from baseline, as well as adverse reactions, were also assessed. Results The objective response rate (ORR) in the observation group (60.87%) was significantly higher than that in the control group (39.13%) (P ＜ 0.05). After 2 cycles of treatment, serum levels of carbohydrate antigen 199 (CA199), carbohydrate antigen 724 (CA724), and carcinoembryonic antigen (CEA) in both groups were lower than before treatment, and the Karnofsky performance status (KPS) scores were higher than before treatment (P ＜ 0.05); the improvements in these indicators and scores were significantly greater in the observation group than in the control group (P ＜ 0.05). After 2 cycles, the CD3⁺ T-cell proportion and CD4⁺/CD8⁺ ratio in the control group were lower than before treatment, whereas the CD3⁺ T-cell proportion, CD4⁺ T-cell proportion, and CD4⁺/CD8⁺ ratio in the observation group were higher than before treatment (P ＜ 0.05); these three immune parameters in the observation group were also higher than those in the control group (P ＜ 0.05). There was no significant difference in the incidence of adverse reactions between the two groups (P ＞ 0.05). Conclusion The combination of sintilimab with oxaliplatin plus capecitabine chemotherapy demonstrates good efficacy in patients with advanced gastric cancer. This regimen can reduce tumor marker levels, improve immune function, and enhance quality of life.