Diphtheria is a very acute contagious and acute upper respiratory tract infection caused by toxigenic strain Corynebacterium diphtheriae. The characteristic pseudomembrane may cause respiratory obstruction, so untreated infection can be fatal. Pathogenesis of Corynebaterium diphtheriae begins with colonization of the upper respiratory tract, followed by production of exotoxin which inactivate EF-2, consequently protein synthesis is block completely and irreversibly, causing cell death. Regulation of diphtheria toxin is controlled by dtxR gene in bacteria activated by Fe system. Nowadays, diphtheria toxin has been introduced as a new method in cancer therapy. Diphtheria toxin can be modified by substitution or germline engineering so that its toxicity is aimed only to cancer cells.