Introduction: The present study aims to assess the efficacy and safety of S-1 plus cisplatin as concurrent chemoradiation (experimental group [EG]) compared with standard concurrent chemoradiation regimens (control group[CG]) in patients with local advanced non-small cell lung cancer. Methods: The Cochrane library, pubmed, and Ovid (elsevier) were retrieved. The included randomized controlled trials (RCT) were evaluated, and the statistical analysis was performed using RevMan 5.3 software. Cochrane handbook was applied to evaluate the methodological quality. Statistical significance was considered as P<.05. Results: There were 5 randomized control trials identified eligible for the meta-analysis. Meta-analysis of the pooled date suggested that overall survival (OS) (HR, 0.81; 95% CI, 0.58-1.13; P=.21, heterogeneity P=1.00, I-2=0%), progressives free survival (PFS) (HR, 0.82; 95% CI, 0.62-1.09; P=.18, heterogeneity P=.83, I-2=0%) and 1,2,3-year OS (1-year OS: RR 1.03; 95% CI: 0.92-1.15, p=0.59), (2-year OS: RR 1.14; 95% CI: 0.98-1.34, P=.09), (3-year OS: RR 1.14; 95% CI: 0.90-1.44, P=.29) were not significantly different. The combination of S-1 and cisplatin had lower grade 3 or 4 leukocytopenia, neutropenia, (RR=0.54, 95% CI: 0.38-0.75, P=.0003; RR=0.23,95% CI: 0.14-0.36, P<.00001;, respectively). The rates of nausea, diarrhea, thrombocytopenia, pneumonitis, anorexia, anemia, febrile neutropenia were much the same in the 2 groups (RR=1.35, 95% CI: 0.68-2.68, P=.38; RR=1.85, 95% CI: 0.61-5.60, P=.28; RR=1.67, 95% CI: 0.88-3.17, P=.12; RR=1.19, 95% CI: 0.44-3.21, P=.73; RR=1.35, 95% CI: 0.682.68, P=.38; RR=0.86, 95% CI: 0.55-1.34, P=.50; RR=0.63, 95% CI: 0.35-1.14, P=.13;, respectively). Conclusions: This meta-analysis of 5 randomized control trails demonstrates that EG results similar OS, PFS, and 1,2,3-year OS, compared with CG, with lower risk of leukocytopenia, neutropenia.