Abstract: The principle of prodrug is classical in medicinal chemistry, which has been applied newly in researches on targeted antitumor drugs as the mechanisms of tumors were continually revealed in recent years. The prodrugs can be designed to improve water solubility and bioavailability or broaden the therapeutic window of parent drugs according to the differences between a normal cell and a tumor cell, such as cell microenvironment, the special enzymes and surface antigens. This article mainly reviews the advances on the application of prodrug in the research of the targeted antitumor drugs in recent years.