Body subunit-targeting therapy is a new strategy for current cancer treatment and a key direction of modern molecular pharmacology research and development. Mitochondria are the sites of energy-yielding and the metabolic centers of cells. Tumor cells have the characteristics of metabolic abnormalities, which makes the development of compounds targeting mitochondria as a new anti-tumor research strategy. In addition, based on the multiple roles of mitochondria in tumor metabolism, targeted mitochondrial therapy drugs are essential to increase drug specificity and reduce adverse effects on normal tissues. This article reviewed the relation between mitochondria and cancer, and summarized the role of the small molecules that are currently used to target mitochondria in cancer treatment, so as to provide a new treatment strategy for cancer.