This study was conducted to analyze a comprehensive panel of single nucleotide polymorphisms (SNPs) in genes in DNA repair and apoptosis pathways to determine the relationship between polymorphisms and treatment outcomes of patients with non-small cell lung cancer (NSCLC) treated with first line paclitaxel-cisplatin chemotherapy. Three hundred eighty two patients with NSCLC were enrolled. Seventy-four SNPs in 48 genes (42 SNPs in 27 DNA repair pathway genes and 32 SNPs in 21 apoptotic pathway genes) were genotyped and their associations with response to chemotherapy and overall survival (OS) were analyzed. Results: Among SNPs in DNA repair genes, BRCA1 rs799917 was significantly associated with both response to chemotherapy and OS. XRCC1 rs25487 exhibited significant association with response to chemotherapy and XPD/ERCC2 rs1052555 with OS. Four SNPs in apoptotic genes (TNFRSF1B rs1061624, BCL2 rs2279115, BIRC5 rs9904341, and CASP8 rs3769818) were significantly associated with OS, but not with response to chemotherapy. When the six SNPs which were associated with OS in individual analysis were combined, OS w decreased as the number of bad genotypes increased (Ptrend=2×10-6). Patients with 3, and 4-6 bad genotypes had a significantly worse OS compared with those carrying 0-2 bad genotypes (aHR=1.54, 95% CI=1.14-2.08, P=0.005; aHR=2.10, 95% CI=1.55-2.85, P=2×10-6, respectively). These findings suggest that the SNPs identified can be used as biomarkers predicting chemotherapy response and survival for NSCLC patients treated with first line paclitaxel-cisplatin.