Pathologies that are caused by asbestos are a public health issue and more particularly, with a worldwide impact, malignant mesothelioma. Macrophage migration inhibitory factor (MIF) is a pro-inflammatory cytokine implicated in various inflammatory diseases and cancers. Through its receptor CD74, MIF provides an interesting link between inflammation, cell growth and tumorigenesis. In a previous report, our research group has identified CD74 as a strong prognostic factor for survival of patients with malignant pleural mesothelioma. In the present study we tried to evaluate the role of MIF / CD74 pathway in malignant pleural mesothelioma studying multiplication of malignant cells genetically modified, by one hand, to down-regulate MIF and CD74 expression using short hairpin RNA (shRNA) and on the other hand to overexpress CD74. Mesothelioma cell lines overexpressing CD74 have been isolated and preliminary results suggested that overexpression of CD74 leads to an increase of proliferation of mesothelioma cells, both in vitro and in ovo assay confirming the potential role of the MIF / CD74 pathway as a key regulator of mesothelioma cell multiplication.