Collectively, NSC 95397 increased the expression of p21 and cleaved caspase-3 in an ERK1/2-dependent manner, indicating that the NSC 95397-induced inhibitory activities, including anti-proliferation and pro-apoptosis, on colon cancer cells might be through inhibition of MKP-1 activity and induction of ERK1/2 phosphorylation. Here, DUSP1 is linked to malignant colon neoplasm.