〔Abstract〕 Objective To investigate the effect of hirsutine combined with oxaliplatin on the antitumor activity of HGC-27 mice with gastric cancer. Methods Gastric cancer HGC-27 tumor-bearing mice model was established. The successfully established tumor-bearing mice were randomly divided into normal control group, model group, oxaliplatin group(10 mg/kg), hirsutine group(10 mg/kg) and combination group(10 mg/kg hirsutine + oxaliplatin 10 mg/kg). The intervention lasted for 2 weeks. The tumor growth of mice in each group was recorded, and the tumor inhibition rate, thymus index and spleen index were calculated. The proportion of CD4+T cells and CD8+T cell subsets in peripheral blood was detected by flow cytometry, and the CD4+/CD8+ratio was calculated. ELISA was used to measure the serum levels of interleukin(IL)-1β, IL-6 and tumor necrosis factor(TNF)-α. HE staining was used to observe the pathological changes in tumor tissues. Western blot was used to detect the protein expression levels of cleaved Caspase-3, Bcl-2 associated X protein(Bax), B-cell lymphoma-2(Bcl-2)and tumor proliferation antigen(Ki67), proliferating cell nuclear antigen(PCNA) in tumor tissues. Results Compared with the control group, the spleen index, thymus index, CD4+T cell ratio and CD4+/CD8+ratio in peripheral blood of the model group decreased(P<0.05), while the proportion of CD8+T cells in peripheral blood and the levels of TNF-α, IL-1β and IL-6 in serum increased(P<0.05). Compared with the model group, the tumor growth in oxaliplatin group, hirsutine group and combined group was significantly inhibited, the volume of tumor cells decreased, the heteromorphism was smaller, and the nucleosomes decreased less. The inhibitory rate, spleen index, thymus index, CD4+T cell ratio and CD4+/CD8+ratio in peripheral blood of the model group increased(P<0.05), the proportion of CD8+T cells in peripheral blood and the levels of TNF-α, IL-1β and IL-6 in serum decreased(P<0.05), while the protein expression levels of Bcl-2, Ki67 and PCNA in tumor tissues decreased and the cleaved Caspase-3 and Bax levels increased(P<0.05). Among them, the combination group of rhynchophylline and oxaliplatin had the most obvious intervention effect. Conclusion Hirsutine can inhibit the proliferation of tumor cells in gastric cancer bearing mice and promote their apoptosis, and has a more significant effect when combined with oxaliplatin.