This study aims to study the role of gefitinib on patients with advanced EGFR-mutation NSCLC (Non-Small Cell Lung Cancer). Totally 115 patients with advanced EGFR-mutation NSCLC treated in our hospital were enrolled as research objects. They were randomly divided into control group (n=57) applied with cisplatin ± pemetrexed and experimental group (n=58) subject to gefitinib± cisplatin ± pemetrexed, both groups were applied with treatment for 4 cycles. Clinical efficacy: The disease control rate (DCR) was 72.41% in the experimental group, which was higher than that of the control group (54.39%, p<0.05); Serum CEA, CYFRA21-1, MMP-9 levels: after 2 and 4 cycles of treatment, serum CEA, CYFRA21-1, and MMP-9 levels were lower in the experimental group (p<0.05); Immune function: after 2 and 4 cycles of treatment, Th1 cells and Th1/Th2 cell levels were higher in the experimental group, while Th2 cell level was higher in the control group (p<0.05); Angiogenesis related indicators: the levels of VEGF, HIF-1α and sCD105 were lower in the experimental group after 2 and 4 cycles of treatment (p<0.05); (5) Adverse reactions: After 2 and 4 cycles of treatment, the levels of VEGF, HIF-1α, and sCD105 were lower in the experimental group (p<0.05). The application of gefitinib in patients with advanced EGFR-mutation NSCLC can help down-regulate CEA, CYFRA21-1, and MMP-9 levels, inhibit angiopoiesis, enhance immune function, and increase disease control rate.