Genetic heterogeneity and metastasis remain the most challenging aspects of cancer treatment. Recent studies have introduced a mutant of diphtheria toxin, cross-reacting material197 (CRM197), as a new promising biological anticancer drug to improve cancer therapy in patients previously resistant to chemotherapy. Weak toxicity of CRM197accounts forthe stimulation ofcell apoptosis and the antitumor effect. Increasing evidence has indicated that the expression of heparin-binding epidermal growth factor-like (HB-EGF) growth factorincreases in most cancer cells, and CRM197 is its specific inhibitor. This study has focused on the structure, properties, and anticancer activity of CRM197.