Background <p>Lung cancer is the leading cause of cancer-related deaths worldwide, with the highest incidence rates in the United States, posing significant public health challenges. Although treatment modalities have advanced to include chemotherapy, radiotherapy, targeted therapies, and immunotherapy, preventive strategies remain underdeveloped. Urgent research into preventive interventions is necessary due to the escalating prevalence of lung cancer, aiming to reduce both mortality rates and healthcare burden.</p> Methods <p>This study employed a Mendelian randomization approach using GWAS summary statistics of immunological features from the GWAS Catalogue to assess the potential causal relationship between T cell lymphocytes, celecoxib, and lung cancer risk. The analysis included various methods such as MR Egger, weighted median, inverse variance weighted, and simple mode to evaluate the robustness of these relationships.</p> Results <p>The analysis revealed a significant association between T cell lymphocytes and lung cancer risk, particularly when using inverse variance weighted and simple mode methods (P-values of 0.002 and 0.000, respectively). The association between celecoxib and lung cancer risk also showed significance in weighted median and inverse variance weighted approaches (P-values of 0.014 and 0.001, respectively). Additionally, specific metabolites such as phosphatidylcholine and sphingolipids were significantly associated with lung cancer risk, potentially offering new biomarkers and targets for the prevention and treatment of lung cancer.</p> Conclusion <p>This study, through Mendelian randomization analysis, unveiled causal relationships between T cell lymphocytes, celecoxib, and specific metabolites with lung cancer risk, providing new potential targets for the prevention and treatment of lung cancer that warrant further investigation.</p>