Objective To investigate the expression of DNA repair gene family members of ERCC1, RRM1 and BRCA1 in tissues of advanced non-small cell lung cancer (NSCLC), and explore its clinical significance. Methods The expression of ERCC1, RRM1 and BRCA1 protein in 122 cases of advanced NSCLC was detected by immunohistochemical methods. The relationship between the expression of ERCC1, RRM1 and BRCA1 protein and the clinical characteristics, response to chemotherapy and prognosis were explored. Results The positive expression of ERCC1, RRM1 and BRCA1 protein in 122 cases was 47.5%, 35.2% and 46.7%, respectively. There was no significant correlation between the positive expression of ERCC1 and RRM1 protein and gender, age, smoking status, ECOG physical status scale score, clinical stages and histological types  (P>0.05), and the expression of BRCA1 protein in females (63.6%) was significantly higher than that in males (40.4%). There was no significant difference in response rates to chemotherapy, median survival time and 1-year survival rate between patients with positive expression of ERCC1 and BRCA1 protein and those with negative expression of ERCC1 and BRCA1 protein (P>0.05). Patients with positive expression of RRM1 protein had significantly lower response rates to chemotherapy and 1-year survival rate than those with negative expression of RRM1 protein (P<0.05). Conclusion The expression of RRM1 protein in cancer tissues is closely related to the response to chemotherapy and prognosis in patients with advanced NSCLC.