Excision-repair-cross-complement-1 (ERCC1) protein expression in tumor cells has been associated with resistance to platinum compounds, the backbone of treatment in NSCLC. In the current study the impact of the tumoral ERCC1 protein expression on the outcome of patients with advanced stage NSCLC treated with platinum-based chemotherapy, was investigated. Ninety-four patients with inoperable stage III-IV NSCLC, treated with platinum-based first-line chemotherapy, were retrospectively analyzed. Pretreatment tumor samples were analyzed for ERCC1 protein expression using immunohistochemistry. Response to treatment, time to tumor progression (TTP), and overall survival (OS) were correlated with patients' clinicopathological characteristics and ERCC1 protein expression on tumor cells. ERCC1 protein low expression was detected in 39 (41.5%) patients and did not correlate with patients' clinicopathological characteristics or response to chemotherapy. However, ERCC1 protein low expression showed a trend for better disease control rate (p = 0.059), longer TTP (5.3 vs. 3.2 months; p = 0.051) and significantly longer OS (18.7 vs. 9.7 months; p = 0.009). ERCC1 could have a role in refining prognosis and thus individualizing chemotherapy for advanced stage NSCLC.