Abstract: NAD(P)H: quinone oxidoreductase 1 (NQO1) is an obligate two-electron reductase that is involved in chemoprotection and can also bioactivate certain antitumor quinones. Levels of NQO1 expression are elevated in tumors particularly in those of the lung, colon and breast in relation to the surrounding normal tissues. The high levels of NQO1 in solid tumors in combination with the ability to reduce many quinone-containing antitumor drugs has drawn our attention to NQO1 as a potential molecular target in cancer treatment. NQO1-targeting drugs are thus expected to achieve high selectivity and specificity to kill tumor cells. This review focuses on discussing the structure-activity relationships of NQO1-targeting antitumor quinones, from which possible future prospectives in this area are presented, in order to ignite and promote the development of NQO1-targeting antitumor drugs.