DNA excision repair gene expression plays a pivotal role in the resistance of platinum-based doublet chemotherapy of nonsmall cell lung cancer (NSCLC) in clinical practice. The aim of this study was to investigate the relationship of the excision repair cross-complementation group 1 (ERCC1) mRNA level in fresh tumor tissue and the efficacy of platinum-based chemotherapy of NSCLC.100 patients diagnosed with NSCLC, including stage IIIB with malignant pleural effusion, stage IV, and recurrent disease, were enrolled in this study. Before clinical treatment, tumor biopsy specimens were collected, and total RNA was purified to analyze ERCC1 mRNA level by real-time polymerase chain reaction assay. All patients were treated with platinum-based third-generation doublet chemotherapy.Patient median age was 60 years. Forty-seven patients had NSCLC with low expression of ERCC1 mRNA, and 53 patients had high expression of ERCC1 mRNA. Although the ERCC1 mRNA level was not correlated with the response rate (p = .665) and progression-free survival (median, 6.4 months vs. 5.5 months; p = .446), the high level of ERCC1 mRNA demonstrated a significant association with poor overall survival (median, 11 months vs. 17 months; p = .02). High level of ERCC1 mRNA was an independent prognostic factor for poor overall survival (p < .001) along with lack of disease control (p < .001).High level of ERCC1 mRNA may serve as a useful prognostic factor for poor outcome in advanced NSCLC patients treated with platinum-based third-generation doublet chemotherapy and may provide important information to guide tailored therapy of NSCLC patients.