This study was to investigate whether the expressions of DNA repair genes ERCC1 (excision repair cross complementing 1), RRM1 (ribonucleotide reductase subunit M1) and BRCA1 (breast cancer 1) affected clinical outcome in patients with NSCLC. Patients with stage IIIb/IV NSCLC were given platinum-based chemotherapy. Messenger RNA expression levels of ERCC1, BRCA1 and RRM1 were determined by real-time polymerase chain reaction with TaqMan probes in the tumor. The relationship between these three genes with chemoresponse and overall survival was analyzed in this study. Eighty-five patients (median age 59, range 30-78) were enrolled into the study. Median overall survival (OS) was 13 months (range 10.8-15.2). Time to progression (TTP) was 6.1 months (range 5.5-6.7). Patients with low ERCC1 expression benefited more from a platinum-containing regimen (P=0.094). Patients with low RRM1 expression benefited more from a gemcitabine-containing regimen. Patients with high BRCA1 expression benefited more from an anti-tubulin-containing regimen (P=0.046). Partial response rate was 42.4%. A statistically significant difference in OS was seen in patients with low ERCC1 levels compared to patients with high ERCC1 ones. (16.5 vs. 10.0 months, P=0.045). A significant relationship was observed between the expression of ERCC1 and BRCA1 and TTP (6.5 vs. 5.1 months, P=0.001, 5.2 vs. 6.5, P=0.019, respectively). High expression of BRCA1 was associated with better survival in the anti-tubulin-containing regimen subgroup (8.7 vs. 13.0, P=0.035). ERCC1, RRM1 and BRCA1 are promising predictive and prognostic biomarkers in advanced non-small cell lung cancer.