CD39 expression on secreting CD4 Tregs was related to an increased risk of small-cell lung cancer (SCLC) (OR, 1.0306 [95% CI, 1.0006–1.0616]), mediated by interleukin (IL)-2 and IL-6 with mediation proportions of 8.43% (95% CI, 0.00005−0.005) and 5.1% (95% CI, 0.00006–0.003), respectively. Here, CD4 is linked to small cell lung carcinoma.