【Abstract】Objective?To analyze the efficacy and safety of programmed death protein 1 (PD-1) inhibitor combined with chemotherapy in the treatment of advanced gastric cancer, and to provide clinical reference. Methods?78?patients with advanced gastric cancer admitted to Jintan District Hospital of Traditional Chinese Medicine from December 2020?to January 2023?were selected as the study objects, and were divided into control group and observation group according to random number table method, with 39?cases in each group. Patients in the control group were treated with oxaliplatin combined with conventional chemotherapy of tegafur, and patients in the observation group were treated with sintilimab on the basis of the control group. The clinical efficacy, levels of tumor markers [carcinoembryonic antigen (CEA), carbohydrate antigen 125 (CA125) and carbohydrate antigen 199 (CA199)],levels of immune function indices and occurrence of adverse reactions were compared between the two groups. Results?The overall clinical efficacy of the observation group was better than that of the control group (P<0.05). After treatment, the levels of CEA, CA125?and CA199?in the two groups were lower than before treatment, and the levels of these tumor markers of the observation group were lower than those of the control group (P<0.05). After treatment, the percentage of CD3+T lymphocytes, the percentage of CD4+T lymphocytes and the ratio of CD4+/CD8+ in the two groups were lower than those before treatment, and the percentage of CD8+T lymphocytes was higher than before treatment, but the percentage of CD3+T lymphocytes, the percentage of CD4+T lymphocytes and the ratio of CD4+/CD8+ in the observation group were higher than those in the control group, and the percentage of CD8+T lymphocytes was lower than that 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?PD-1?inhibitor combined with chemotherapy has a significant effect in the treatment of advanced gastric cancer, which can further reduce the level of tumor markers in patients and improve immune function, and has good safety, which is worthy of clinical application.