Willow bark extracts have been used for centuries as a natural pain killer. Recently their potential as anticancer agents has been reported. We have shown the high antioxidant activity, phenolic and flavonoid content in the ethanolic extract of bark (EEB) from Salix aegyptiaca, a species endogenous to the Middle East. We have also reported that incubation with EEB resulted in a reduction in cell proliferation through the induction of apoptosis and cell cycle arrest via the inhibition of phosphatidyl inositol 3kinase/Protein kinase B and mitogen activated protein kinases signaling pathways as strongly as commercial inhibitors. The current study demonstrates the robust inhibition of anchorage-independent growth, motility, migration, and adhesion of colon cancer cell lines HCT-116 and HT-29 by EEB. These in vitro functional changes were accompanied by a restoration of E-cadherin expression, a reduction in EGFR, SNAI1, SNAI2, and Twist1 and the matrix metalloproteases MMP9 and MMP2. Many of these proteins are involved in the process of epithelial to mesenchymal transition, which is considered as a critical step in the progression of noninvasive tumor cells into malignant, metastatic carcinomas. We therefore propose that EEB from Salix aegyptiaca is a potent nutraceutical causing cancer chemoprevention by inhibiting epithelial to mesenchymal transition and can be consumed for its health promoting effects.