In this study, targeting dCAS9‐MMP‐9 to a promoter region triggered H3NT proteolysis and resulted in reactivation of target genes in MMP‐9‐depleted colon cancer cells. On the other hand, H3NT proteolysis by dCAS9‐MMP‐9 in the coding region was not sufficient for the establishment of active chromatin environment at target genes. Here, MMP9 is linked to malignant colon neoplasm.