Objective:To compare the clinical efficacy of chemotherapy in late stage NSCLC by two types of methodologies:selective gemcitabine and cisplatin (GP)treatment based on ERCC1 and RRM1 low expression vs. non-selective standard treatment. Methods:This prospective,open study was based on whether target tissue is appropriate for immunohistochemical detection of molecular markers. The enrolled late stage NSCLC patients were divided into two groups,including the group A:low expression in ERCC1 and RRM1 markers,and the group B:no molecular marker pre-selection. After 4-6 weeks treatment with GP chemotherapy,the clinical outcome,progressive-free survival(PFS),overall survival(OS)and toxic/adverse reactions from chemotherapy were compared between the two groups. Results:The Group A (GP method based on ERCC1 and RRM1)has shown significant improvement in efficacy (χ2 = 5.377,P = 0.02) as well as statistically significant extension in PFS (P = 0.03)comparing to the Group B. There was no significant difference in OS and toxic/adverse reactions between the two groups. Conclusion:GP chemotherapy method which selected based on ERCC1 and RRM1 low expression could significantly improve the efficacy and PFS in patients of NSCLC late stage.