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Objective To explore the clinical efficacy and immunomodulatory effects of anlotinib capsule combined with GP regimen in the treatment of advanced non-small cell lung cancer(NSCLC). Methods Forty patients with advanced NSCLC admitted to Nanjing Jiangbei Hospital from October 2020 to October 2022 were divided into two groups using a random number table method. The chemotherapy group ( n=20) was treated with GP regimen, and the combined group ( n=20) was treated with anlotinib capsule on the basis of the chemotherapy group. The short-term efficacy, immune function indexes (CD3+, CD4+, CD4+/CD8+, NK cells) and FACT-L scale scores of the two groups were detected before treatment and 4 months after treatment, and the incidence of adverse reactions was recorded. Results After treatment, the disease control rate (95.00% vs 70.00%, χ2=4.329, P=0.037) and the total effective rate (70.00% vs 30.00%, χ2=6.400, P=0.011) of the combined group were better than those of the chemotherapy group. After treatment, CD3+, CD4+, CD4+/CD8+ , NK cells and FACT-L and KPS scores in the two groups were increased, and those in the combined group were higher than those in the chemotherapy group (P<0.05). There was no significant difference in the total incidence of adverse reactions between the combined group and the chemotherapy group (45.00% vs 30.00%, P>0.05). Conclusion Anlotinib capsule+GP regimen can improve the overall therapeutic effect of patients with advanced NSCLC, not only improve the function of the patient ‘s immune system, but also has high safety, and has certain clinical application value.