Objective To study the effects of Tegafur-based Three-Drug Regimen combined Apatinib on immune function and serum cytokine levels in patients with advanced gastric cancer. Methods A total of 89 patients with advanced gastric cancer in our hospital were divided by random number table method. 44 patients in the conventional group were treated with Oxaliplatin and Tegafur, and 45 patients in the study group were treated with Apatinib. Serum tumor marker levels, serum cytokine levels, immune function and adverse reactions were compared between the two groups.Results The levels of carcinoembryonic antigen (CEA) and carbohydrate antigen 125(CA125) in the study group were lower than those in the conventional group (P < 0.05). After treatment, the serum levels of γ-interferon (IFN-γ), normal epithelial cell specific -1 gene (NES1), interleukin-10 (IL-10) and tumor necrosis factor-α (TNF-α) in the study group were higher than those in the conventional group (P < 0.05). The level of T lymphocytes (CD8+) in the study group was lower than that in the conventional group after treatment, and the levels of CD3+ and CD4+ were higher than those in the conventional group (P < 0.05). Conclusion The three-drug regimen based on Tegafur combined with Apatinib can effectively improve the immune function of patients with advanced gastric cancer, improve the level of serum cytokines, and reduce the level of serum tumor markers, with high safety.