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We investigated inhibitory effects of apple polyphenol (AP) in vitro and in vivo. AP significantly suppressed migration, invasion, colony formation and adhesion of DLD-1 cells. AP also reduced expression of tubulin and F-actin, and consequently altered the cytoskeleton structure. AP reduced expression of focal adhesion kinase (FAK) but not talin, α-actinin and vinculin. The activation of FAK downstream effectors paxillin, Src, PI3K and Akt were also inhibited by AP. Moreover, AP inhibited activity but not expression level of FAK-associated GTPase Rac-1, Cdc42 and Rho A. The inhibition of FAK expression by AP was proteasome-independent, which was attributed to interfered binding of Snail to a putative E-box on the FAK promoter. Anti-tumoral and anti-metastatic effects of AP were also demonstrated in vivo. Collectively, AP significantly inhibited motility of DLD-1 cells via disruption of interaction between Snail and the FAK promoter and consequently diminished tumorigenesis and metastasis of DLD-1 cells.