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Abstract Background Considering the effect of smoking on tumor immunity, we attempted to investigate the impact of smoking history on the prognostic value of circulating naïve and memory CD4+ and CD8+ T cells in advanced non-small cell lung cancer (NSCLC) treated with chemo(radio)therapy. Methods Of 196 histologically confirmed advanced NSCLC, 98 eligible ones were enrolled. Naïve and memory CD4+ and CD8+ T cells from peripheral blood were measured by flow cytometry. Kaplan–Meier curves helped estimate patients’ survival. The uni- and multivariate Cox proportional hazards regression model was employed in the assessment of the prognostic value of factors. Results Multivariate survival analyses showed that peripheral naïve CD4+ T cells independently predicted favorable overall survival (OS) in ever smokers with advanced NSCLC (P = 0.007), but unfavorable OS in never smokers with the same ailment (P = 0.012). Ever smokers presented a different distribution of naïve and memory T cells: low expression levels of naïve CD4+ T (P = 0.005), naïve CD8+ T (P = 0.031), CD4+ naïve/memory ratio (P = 0.020), and CD8+ naïve/memory ratio (P = 0.019), and high distributions of memory CD4 + T (P = 0.004), memory CD8 + T (P = 0.034), and naïve CD8/CD4 ratio (P = 0.020), when compared to never smokers. Conclusions We revealed the impact of cigarette-smoking on peripheral naïve CD4+ T cells’ prognostic value in advanced NSCLC patients. These results could help in refining personalized treatment for advanced NSCLC patients.