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Objective We conducted a perspective study to investigate the association between mRNA expression quantities of ERCC1, BRCA1, RRM1 and RRM2 and response to chemotherapy and clinical outcome of advance Non-Small Cell Lung Cancer.(NSCLC). Methods Two hundred eight patients who were diagnosed as advanced stage NSCLC were included in our study. A fluorescence-based and real-time detection method was used to determine the relative cDNA quantification for ERCC1, BRCA1, RRM1 and RRM2, and β-actin was used as the reference gene. Results The median expression levels of ERCC1, BRCA1, RRM1 and RRM2 mRNA were 0.67±0.17, 0.095±0.012, 0.24±0.17 and 2.45±0.32, respectively. Our study found that the low ERCC1 (OR=1.82, 95% CI=1.01-3.20) and Low BRCA1 (OR=2.53, 95%CI=1.38-4.64) mRNA expression was more likely to response to chemotherapy when compared with high expression, respectively. Multivariate Cox regression analysis indicated that patients with low mRNA expression of ERCC1 and BRCA1 attained 0.43 (OR=0.43, 95%CI=0.27-0.89) and 0.37 (OR=0.37, 95%CI=0.22-0.66) fold risk of death from NSCLC. However, we found RMM1 and RRM2 mRNA expression could not influence the response to chemotherapy and clinical outcome of NSCLC. Conclusion ERCC1 and BRCA1 mRNA expression could be important predictive markers for individualized platinum-based chemotherapy for NSCLC patients.