Objective: The aim of the study was to compare the efficacies and toxicities of non-platinum doublets (doublets group) with a non-platinum single agent (single-agent group) in previously untreated advanced non-small cell lung cancer (NSCLC) patients with elderly age and/or poor performance status (PS). Methods: The PubMed database was screened. Subsequently, the hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS), relative risks (RRs) for overall response rate (ORR) and one-year survival, and odds ratios (ORs) for the different types of toxicities were pooled using the Review Manager 5.0 package. Results: This study comprised of 1427 patients enrolled in four randomized controlled trials. The pooled HR showed that the doublet group could increase ORR (P = 0.002) with no heterogeneity (P = 0.64), and might improve OS (P = 0.01 / P = 0.06) with heterogeneity (P < 0.001). There was no significant difference in PFS (P = 0.16) and one-year survival (P = 0.25) between two treatment groups. The doublet group led to more grade 3/4 neutropenia and thrombocytopenia than the single-agent group (P = 0.02 and P = 0.000, respectively). The incidences of grade 3/4 anemia, vomiting, mucositis, constipation, diarrhea, neurotoxicity, allergy, and fatigue between the two treatment groups were insignificant. Conclusion: Except for neutropenia and thrombocytopenia, the non-platinum doublets could increase ORR, and might improve OS for NSCLC patients with elderly age and/or poor PS without addition of more side effects; however, the doublets showed an increased rate of neutropenia and thrombocytopenia. The addition of doublets may not improve PFS and one-year survival. Objective: The aim of the study was to compare the efficacies and toxicities of non-platinum doublets (doublets group) with a non-platinum single agent (single-agent group) in previously untreated advanced non-small cell lung cancer (NSCLC) patients with the age and / or poor performance status (PS). Methods: The PubMed database was screened. The hazard ratios (HRs) for overall survival (OS) and progression-free survival overall response rate (ORR) and one-year survival, and odds ratios (ORs) for the different types of toxicities were pooled using the Review Manager 5.0 package. Results: This study comprised 1427 patients enrolled in four randomized controlled trials. The pooled HR showed that the doublet group could increase ORR (P = 0.002) with no heterogeneity (P = 0.64), and might improve OS (P = 0.01 / P = 0.06) with heterogeneity PFS (P = 0.16) and one-year survival (P = 0.25) b The doublet group led to more grade 3/4 neutropenia and thrombocytopenia than the single-agent group (P = 0.02 and P = 0.000, respectively). The incidences of grade 3/4 anemia, vomiting, mucositis, constipation , diarrhea, neurotoxicity, allergy, and fatigue between the two treatment groups were insignificant. Conclusion: Except for neutropenia and thrombocytopenia, the non-platinum doublets could increase ORR, and might improve OS for NSCLC patients with elderly age and / or poor PS without however, the doublets showed an increased rate of neutropenia and thrombocytopenia. The addition of doublets may not improve PFS and one-year survival.