BACKGROUND To determine prognostic value of excision repair cross-complementation 1 (ERCC1) in patients with malignant pleural mesothelioma (MPM). METHODS The study included 60 patients with MPM who were diagnosed and treated in the Radiation Oncology Department of Kayseri Teaching Hospital and Medical Oncology Department of Erciyes University, Medicine School between 2005 and 2013. By using immunohistochemical methods, ERCC1 expression in biopsy specimens was evaluated. We retrospectively assessed whether there is a correlation between ERCC1 and response to anti-neoplastic therapy or survival. RESULTS There were 50 men and 10 women with median age of 62 years (range: 39-83). Histological type was epithelial mesothelioma in the majority of the cases (85%), most commonly presenting in stage four. Of the cases, 20 (33%) received radiotherapy, 60 (%100) received first-line chemotherapy and 15 (%25) received second-line chemotherapy. In the assessment after therapy, it was found that there was partial response in 12 cases (20%), stable disease in 19 cases (31.4%) and progression in 25 cases (41.7%). ERCC1 was positive in 43% of the cases. Mean OS was 11.7 months and mean DFS was 9.5 months in ERCC1-positive cases regardless of therapy, while they were 19.2 months and 17.1 months in ERCC1-negative cases, respectively. The difference was found to be significant (p<0.05). In univariate analysis, stage, comorbidity, response to treatment and ERCC1 expression were found to be significantly associated with OS (p=0.083; p=0.043; p=0.041; p=0.050). In multivariate analysis, response to treatment remained to be significant for OS (p=0.005). In univariate and multivariate analyses, response to treatment and ERCC1 were found to be significantly associated with DFS (p=0.049; p=0.041). CONCLUSIONS ERCC1 was identified as poor prognostic factor in patients with MPM.