Various impacts of Matrix Metalloproteinases (MMPs) were reported in many cancer types. Particularly, MMPs are involved in extracellular matrix destruction which is required cancer cells to make an invasion. Gene polymorphisms which are thought to affect expressions levels of MMPs are widely studied to determine their influence on cancer. In this study, we aimed to investigate the association of gene polymorphism frequencies of MMP2 C1306T and MMP9 C1562T in Malignant Mesothelioma (MM), other metastatic cancers to pleura and benign pleural diseases. DNA extracted from pleural tissues of 195 subjects (MM, other metastatic cancers to pleura and benign pleural diseases). MMP2 C1306T and MMP9 C1562T polymorphisms genotyped using restriction fragment length polymorphism (RFLP) method. We found no significant difference in genotype frequencies of MMP2 C1306T, MMP9 C1562T between subjects except for MMP2 C1306T CT genotypes were high in MM when compared to benign pleural diseases group. We recommend extensive mutation and polymorphism scan including whole exomes of these genes.