CD4+ tumour infiltrating lymphocytes (TILs) have been found to produce a marked effect in anti-tumour immunity. In the present study, the authors explored the predictive value of CD4+ TILs in patients with non-small cell lung cancer (NSCLC) receiving PD-1/PD-L1 inhibitors therapy. The authors searched Cochrane, Embase, PubMed, and the Web of Science with a November 2023 deadline. This study followed the requirements of the preferred reporting items for systematic reviews and meta-analyses (PRISMA). The data were analysed by Stata MP17.0 software. Endpoints included objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). In total, 13 studies ultimately met the inclusion criteria. Findings showed high levels of CD4+ TILs in tumour tissue were correlated with better ORR (OR = 1.78, 95% CI: 1.15-2.76, p = 0.010) in NSCLC patients, rather than PFS (HR = 0.82, 95% CI: 0.65-1.05, p = 0.11) and OS (HR = 0.86, 95% CI: 0.69-1.09, p = 0.217). In addition, high levels of peripheral blood CD4+ T cells correlated with better PFS (HR = 0.66, 95% CI: 0.46-0.94, p = 0.02), rather than OS (HR = 0.90, 95% CI: 0.69-1.19, p = 0.461). The results demonstrated that high CD4+ TILs in tumour tissue can predict better ORR for NSCLC patients receiving PD-1/PD-L1 inhibitors, and high peripheral blood CD4+ T cells can predict better PFS. Key Words: CD4-positive T-lymphocytes, Immune checkpoint inhibitors, Non-small cell lung cancer, Peripheral blood, Prognosis, Tumour-infiltrating.