Background The expression of the co-stimulatory molecule CD28 and death receptor CD95 on T cells, which change with age, are considered as important immunological parameters of immunosenescence. It is well established that CD28 and CD95 are associated with tumorgenesis and tumor progression, but the relationship between the age-related changes of these two immunological markers and cancer in the elderly is largely unknown.Methods The levels of CD28 and CD95 mRNA in peripheral blood mononuclear cells (PBMCs) from sixty-three elderly patients (aged 60 years) with primary non-small cell lung cancer (NSCLC) were analyzed by real-time fluorescence-based quantitative polymerase chain reaction (FQ-PCR). In addition, twenty young patients (aged <60 years) with NSCLC, thirty elderly healthy donors and thirty young healthy donors were enrolled as controls. Results CD28 mRNA levels were significantly lower and CD95 mRNA levels were significantly higher in elderly patients with NSCLC than in the other groups. Similar results were found in elderly healthy donors comparing with young healthy donors. By Logistic regression analysis an increased risk of NSCLC was markedly associated with aging, down-regulation of CD28 mRNA and up-regulation of CD95 mRNA, and CD28 mRNA had an obvious negative correlation with the CD95 mRNA. In addition, the mRNA levels of CD28 and CD95 in the peripheral blood of the elderly patients was closely associated with the tumor node metastasis (TNM) stages, grade of cell differentiation and lymph node metastasis status, but not related to pathological types.Conclusions The results suggest a close relationship between T cell senescence and NSCLC tumour progress in the elderly, and that up-regulation of CD28 mRNA or down-regulation of CD95 mRNA in peripheral blood T cells may play an important role in inhibiting oncogenesis and development of primary NSCLC in the elderly.