Extracellular matrix (ECM) degradation enzymes, such as matrix metalloproteinases (MMPs) and plasminogen activators, are important factors in cancer invasion and metastasis, because invasion and metastasis of cancer cells require destruction of mesenchymal collagen or the endothelial basement membrane. Moreover, recent studies have shown that ECM degradation enzymes play important roles in cancer cell proliferation, cancer escape from the immune system, and tumor angiogenesis. ECM degradation enzymes, especially some MMPs, are good targets for anticancer metastatic therapy. Numerous anti-MMP agents have been developed and phase III clinical trials in advanced cancers ongoing. Successful control of MMPs induced by cancer cells will prevent liver metastasis of colorectal cancer.