Esteazeh, seeking refuge in God is one of the divine prayers mentioned in the Holy Quran which Muslims resort to when being tempted by the devil.Investigating the woks of Molla Sadra, we can discover that he has approached this topic from his own special fashion. In his interpretation of Quran, we can find topics about isti’azih, musta’iz (the one seeking asylum to God), musta’azun bih (the one we seek asylum to), musta’azun minh (the one we seek asylum from), ma yasta’azu li ajlih (the thing for which we seek asylum to God), and the necessity of isti’azih. According to Mulla Sadra, isti’azih is based on five pillars which include: isti’azeh, musta’iz, musta’azun bih, musta`azun minh, ma yasta’azu li ajli. In this article ist’azih and its effects on human being’s spiritual perfection according to the rational and mystical viewpoint of Mulla Sadra has been studied.