This study aimed to examine the effectiveness of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) in treating patients with nonsmall cell lung cancer (NSCLC), and the association between clinical characteristics and effectiveness. This retrospective study included 140 patients with NSCLC admitted to our hospital between July 2020 and July 2022. The patients were categorized into 2 groups according to the treatment that they received: a comparison group (67 patients) and a research group (73 patients). The comparison group received conventional chemotherapy, and the research group received conventional chemotherapy and EGFR-TKI-targeted therapy. The immune and tumor marker levels, clinical response, and relationship between clinical characteristics and response to therapy were compared between the 2 groups before and after treatment. After treatment, the levels of neuron-specific enolase and carcinoembryonic antigen (CEA) and CD8+ count were significantly lower, and forced vital capacity, forced expiratory volume in 1 second, and CD4+ count were significantly higher in the research group than in the comparison group. After treatment, the clinical effectiveness in the 2 groups significantly improved, and the disease control rate in the research group was significantly higher than that in the comparison group (89% vs 69%, P = .014). The bivariate analysis revealed that smoking history, ECOG Performance Status score, and CEA level were significantly associated with clinical effectiveness. Conventional chemotherapy combined with EGFR-TKI-targeted therapy is effective in patients with NSCLC and has a clinically significant effect on improving patients’ immune function and lung function.