Malignant pleural mesothelioma (MPM) is a malignant tumor of the mesothelial lining of the thorax. It has been related to frequent exposure to asbestos. Diagnosis of malignant pleural mesothelioma is considered a criticizing problem for clinicians. Early diagnosis and sufficient surgical excision of MPM are considered the cornerstone success factors for the management of early MPM. Glutathione peroxidase-1 (GPX1) is an intracellular protein found to be extensively distributed in all cells, and it belongs to the GPX group. In the current study, we included ninety-eight patients with MPM that underwent surgery at the Zagazig University Hospital in Egypt. We assessed GPX1 gene expression level as it was thought to be related to pathogenicity of cancer in a variety of malignant tumors. We observed a significant elevation in GPX1-mRNA levels in MPM relative to the nearby normal pleural tissues. It was found to be of important diagnostic specificity in the differentiation of MPM from normal tissues. Moreover, we studied the survival of patients in correlation to the GPX1 expression levels and we reported that median overall survival was about 16 months in patients with high GPX1 expression levels, while it was found to be about 40 months in low GPX1 levels.