V2O5-WO3/TiO2 catalyst was used to NH3-SCR technology to control NOx emission from the waste incineration plants. While the flue gas always contains toxic substances, which resulting in the deactivation of catalysts. Most studies only reported the toxic effect of one single component. Actually, the flue gas contains multiple toxic components. Hence, the effect of combination poisoning of KCl and ZnCl2 on the activity and physicochemical properties of V2O5-WO3/TiO2 catalyst were analyzed to reveal the structure-activity relationship of the catalyst. The activity results showed that the co-existence of KCl and ZnCl2 would aggravate the toxic effect. The characterization results showed that K+, Zn2+, and Cl– would bond with V-OH and OV active sites, thereby destroying active acid sites (V-OH) and V5+⇄V4+ redox cycle. In which, KCl had a greater negative effect on active acid sites (V-OH), while ZnCl2 had a greater negative effect on the redox sites (OV). The active acid sites and redox sites on the surface of V2O5-WO3/TiO2 catalyst were further destroyed when KCl and ZnCl2 was co-existence. Moreover, the co-existence of KCl and ZnCl2 would promote the formation of stable and low-activity nitrates and nitro species, thereby inhibiting NOx participation in NH3-SCR reaction. Eley-Rideal (E-R) mechanism exists on V2O5-WO3/TiO2 catalyst, and the combination poisoning of KCl and ZnCl2 does not change the reaction mechanism.