Immune escape and immunosuppression are the main reasons that affect the efficacy of lung cancer treatment. This study mainly explored the mechanism of polystyrene nanoparticles-mediated astragalus polysaccharides (APS-PSNPs) in improving immune function of mice with lung cancer. APS-PSNPs were constructed and a lung cancer mouse model was established to observe tumor volume and mass, and pathological changes by HE staining. Levels of TNF-a/IFN-γ/IL-2/IL-6 in mouse spleen tissue were detected by ELISA, the lymphocyte CD3+, CD4+, CD8+ apoptosis levels were tested along with analysis of the expression of TLR4, MyD88, and NF-κB. (1) APS-PSNPs were successfully constructed. (2) APS-PSNPs had a good tumor suppressor effect on lung cancer, inhibited IL-2 expression, and improved immune function of lung cancer mice. (3) TLR4, MyD88, NF-κB levels in lung cancer mice were upregulated, and MyD88 and NF-κB levels decreased after inhibiting TLR4 expression with improved pathological changes of lung. (4) APS-PSNPs effectively reduced TLR4, MyD88, NF-κB levels. The levels of TNF-a/IFN-γ/IL-2/IL-6 decreased in APS-PSNPs+TAK-242 group, the apoptosis of spleen lymphocyte subsets CD3+, CD4+, CD8+ was significantly weakened, and the degree of fibrosis of lung tumor tissue was significantly lower. APS-PSNPs, with good anti-lung cancer value, can improve immune function, inhibit lung tissue lesions, and inhibit tumor progression to a certain extent. This process is related to reducing TLR4/MyD88/NF-κB activity and down-regulating IL-2, etc.