Dieckol, a polyphenol compound extracted from Brown algae, Ecklonia cava, is known to have anti-inflammatory and anti-tumorigenic activities. However, the underlying molecular mechanism by which dieckol regulates cancer cell growth and proliferation remains elusive. Here we report that dieckol extracted from Ecklonia cava inhibited 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced human hepatocellular carcinoma SK-Hep1 cell motility, and that dieckol decreased extracellular signal-regulated kinases 1/2 and c-Jun N-terminal kinases (JNKs) activities, but not p38 Mitogen-Activated Protein Kinase (MAPK), in dose-dependent manner. Dieckol reduced TPA-induced activator protein-1 transcriptional activity. TPA-induced matrix metalloproteinase-9 (MMP-9) activity was greatly reduced in SK-Hep1 cells by treatment of dieckol. These findings suggest that dieckol functions as a potent inhibitor for tumor promoter-mediated MAPK signaling pathways leading to Activator Protein 1 (AP-1) and MMP-9 activation thereby regulates cancer cell motility.