The rule of negation of the mustache is one of the fundamental and strategic principles in Shiite political jurisprudence that explains the legitimacy and necessity of political resistance against various forms of domination. Political resistance in this framework is defined not only as a tactical response, but also as a religious and social obligation to preserve the dignity, independence, and national sovereignty of the Islamic society in the face of the influence and domination of foreigners (political, economic, military, and cultural). The rule of negation of the mustache, derived from verse 141 of Surah An-Nisa and substantiated by the threefold evidence of tradition, consensus, and reason, constitutes the main theoretical basis of this approach. This rule emphasizes the impermissibility of legislating and forging any ruling by the holy lawgiver that would lead to granting "mustache" to infidels over believers. The present article, after analyzing the evidence and provisions of the rule of negation of the mustache, explains its pivotal role in legitimizing and requiring political resistance. The findings of the research show that the rule of negating the mustache, while considering any foreign domination and influence illegitimate from a religious perspective, proves the necessity of active struggle and resistance to repel and eliminate this domination. This jurisprudential principle, in practice, plays a role as a strategic paradigm for formulating the macro policies of the Islamic Republic of Iran.