Abstract: Selective catalytic reduction (SCR) is currently the most widely employed technology for NO_x removal in coal-fired power plants. To address the catalyst deactivation caused by multiple impurities in flue gas from biomass co-firing, the individual and combined poisoning effects of potassium (K), phosphorus (P), and chlorine (Cl) on commercial V₂O₅–WO₃/TiO₂ denitration catalysts were systematically investigated, with particular emphasis on the underlying microscopic mechanisms. The results demonstrate that K alone induces irreversible catalyst deactivation by extensively neutralizing strong surface acid sites and promoting the excessive reduction of vanadium and tungsten species. In the presence of multiple impurities, K and P exhibit a pronounced synergistic poisoning effect, reducing the maximum NO_x conversion of the commercial catalyst to only 18%, corresponding to a decrease of approximately 81 percentage points and resulting in nearly complete deactivation. Interestingly, the introduction of Cl restores the maximum NO_x conversion of the K- and P-poisoned catalyst to approximately 60%. Combined analyses of surface acidity and oxidation states of active species reveal a significant antagonistic effect of Cl against K–P-induced poisoning. Owing to its high electronegativity, Cl facilitates the redistribution of excess electrons introduced by K, thereby weakening the interaction between K and surface acid sites while maintaining the electron-transfer pathways essential for the redox cycling of active species. Consequently, the necessary pathways for reactant adsorption and activation are preserved. In the context of biomass co-firing in coal-fired power plants, these findings provide mechanistic insights into the complex interplay between electron redistribution and surface acid-site reconstruction in multi-impurity environments, offering a theoretical basis for developing commercial denitration catalysts with high catalytic activity and enhanced resistance to synergistic poisoning by multiple impurities.