Sodium butyrate (SB)-C-4 saturated fatty acids are present in the human bowel membrane in high concentration (2 mM) as food metabolites. Here, we focused on the role of SB on cancer cell motility and invasion. SB inhibited human fibrosarcoma (HT1080) and human glioblastoma (A172) cell motility and invasiveness, decreased cell growth in a dose-dependent fashion. SB also affected the morphology of the HT1080 and the A172 cells, namely spread out. Phosphorylation levels of focal adhesion kinase (FAK, pY577 and pY397 sites) were increased. All of these biological effects of SB were reversible, and recovered after withdrawal. In addition, HT1080 cells and A172 cells treated with SB showed positivity for senescence-associated b-gal (SA-b-gal) staining with elevated expression levels of p53 and p21 proteins in a dose-dependent manner. Further, the proteosome inhibitor, MG-132 decreased 2D cell growth and inhibited motility and, invasiveness of the HT1080 and A172 cells, and showed similar of all these biological effects of SB. Collectively, SB induced cellular senescence, inhibited invasion and growth, and would be a good candidate for anti-invasive therapy without severe adverse effects.