KD was firstly applied to treat cerebral diseases, such as cerebral glioma, epilepsy and so on. Researches of last two decades found that chronic inflammation, elevated blood glucose were closely related to tumor development. Regular exercise and fasting could lower blood glucose, increase the concentration of plasma ketone bodies and reduce the inflammatory response. KD, characterized as high fat and very low carbohydrate could evoke a physiological state similar to exercise or fasting. These promote its possible use in treatment of metabolic diseases. With the intensive studies of metabolism and nutrition of cancer, there were growing evidences indicating cellular metabolism plays a very important role in the occurrence and development of tumor. With the application of various experimental methods and the breakthrough of signaling pathways, researchers believed altered metabolism of cancer cells is a potential target for therapeutic intervention. Thus, the anti-tumor effect of KD had become a research focus in recent years. Cancer cells depend on glucose as main energy, and the patients themselves need to consume more fat and protein, accordingly, the ketogenic theory providing enough protein and fat, limiting glucose can treat cancer theoretically. The KD making use of the characteristics of mitochondrial defects and glucose dependent of tumor cells, through suppressing inflammation, enhancing immune response, improving the ability of antioxidant stress, regulating related signal pathway, etc., inhibits tumor growth, improves patients’ quality of life, prolonges the survival of patients and enhances the sensitivity to radiotherapy and chemotherapy. These mechanisms provided a theoretical basis for the application of KD in cancer treatment. However, some mechanisms were not fully elucidated, further basic research and clinical trials is needed to confirm.