Epithelial-mesenchymal transition (EMT) is a process in which epithelial cells lose their ability for cell to cell adhesion, causing a pheno-conversion of epithelial cells into the migratory phenotype of mesenchymal cells. EMT is induced in part by Snai1 expression which directly represses E-Cadherin transcription. E-Cadherin plays an integral role in forming adherens junctions that bind cells together. The EMT process plays an essential role in physiological trans-differentiation of cells during development and contributes to pathological responses and cancer progression. Snai1 is a zinc-finger transcription factor that triggers EMT during embryonic development as well as in pathological processes such as tumors or fibrosis. Scleraxis is a transcription factor that significantly increases the expression of important extracellular matrix genes such as type I collagen and the contractile protein α-smooth muscle actin (α -SMA), which are key players of the fibrotic process. Our published data suggests that Scleraxis overexpression in the adenocarcinomic human alveolar basal epithelial cells (A549 cells) down-regulates some epithelial markers while up-regulating mesenchymal markers, thus contributing to EMT. Here we show that Scleraxis regulates the transcriptional activity of the Snai1 gene through direct binding to E-box sequences within its promoter. Additionally, we show that Scleraxis enhances EMT progression mediated by its interaction with the Snai1 gene promoter. These findings suggest that Scleraxis –Snai1 axis is a potential therapeutic candidate that could be targeted in pathological processes where EMT is elevated.