Present paper has studied Ayatollah Khamenei`s view on political comment of Quranic concepts during IRI. The purpose lies in awareness with Ayatollah Khamenei`s approach of political comment of Quranic concepts and its effects in IRI. The method of study is descriptive-analytic. When analyzing political comment of the holy Quran, in addition to the holy text of the Quran, political, social and mental have been effective in appearance of political comment of Quranic concepts and their application in IRI. In this approach, religion has been known to be answering all human needs in individual, social and political fields. Before revolution, Ayatollah Khamenei has used such Quranic teachings as tawhid, nobowwat and imamat to support revolutionary movement against present condition (inner despotism and foreign prominence). Quranic political comment after revolution has been focused on the structure of political system, fighting against prominence system and Muslims unity.