Failure of actions is one of the important theological topics which has been mentioned in the Quran’s Verses including the holy verse “If thou ascribe a partner to Allah thy work will fail and thou indeed wilt be among the losers.” In this verse which is addressed to the holy prophet and the previous prophets, polytheism is deemed as the factor of failure of actions. The possibility of polytheism and failure of the prophets’ actions and its incompatibility with infallibility has been one of the challenges that prophets and commentators have been confronted by. To Imamieh Approach, the Mu’tazilah’s viewpoint on failure of actions is invalid; therefore, the failure mentioned in the Quran has a different meaning with its theological meaning. Lack of discrimination between its Quranic application and what is common among the theologians has created many challenges in regard to semantics of failure, failure-dependents and the reasons of failure. Studying the contents of the above-mentioned verse and enjoying the commentators’ ideas especially Amin Al-Islam Tabarsi, the paper is an attempt to investigate two major approaches about possibility of polytheism and failure of actions of the prophets and believers, then, it explains the Quranic meaning of failure and its contradiction with the theological meaning and also to investigate the reasons of failure, failure-dependents, and the manner of such dependency to infidels and disbelievers.