Objective:To investigate the effects of EGFR-TKI combined chemotherapy on immune function, tumor markers and oxidative stress in patients with stage-IV lung adenocarcinoma.Methods:This retrospective observational study included 116 patients with stage-IV lung adenocarcinoma, treated in The First Affiliated Hospital of Soochow University from January 2021 to January 2022. According to the treatment records, 60 patients that received pemetrexed + cisplatin for four courses were set as a Control-group and 56 patients that received EGFR-TKI + pemetrexed + cisplatin for four courses were set as an Observation-group. Changes in immune function, tumor marker levels and oxidative stress level in the two groups were analyzed and compared.Results:After the treatment, levels of CD3+, CD4+, IgG and IgM in the Control-group were significantly lower than those before the treatment. EGFR-TKI + pemetrexed + cisplatin resulted in levels of CD3+, CD4+, IgG and IgM higher than before the treatment, and compared to the Control-group (p<0.001). After the treatment, the levels of NSE, serum CEA, serum CA125, CYFEA21-1 in both groups were significantly lower than those before treatment, and lower in the Observation-group (p<0.001). After the treatment, VEGF and MMP9 levels in both groups were significantly lower than those before treatment, and markedly lower in the Observation-group (p<0.001).Conclusion:Compared with systemic chemotherapy, EGFR-TKI targeted combined chemotherapy for stage-IV lung adenocarcinoma is associated with enhanced immune function of patients. It more effectively inhibits the growth and proliferation of tumor cells and reduces the level of oxidative stress.