CaO was the inevitable cause of V2O5-WO3-TiO2 catalyst (VWTi) poisoning in cement kilns. The significant reduction in NO conversion was due to the combination of CaO and active species of the vanadium-based catalyst. In this work, the VWTi catalysts were modified with different contents of Cu and P to improve resistance to CaO, thereby extending the service life of catalysts in cement kilns. By doping Cu and P, the Ca-VWCu3P5Ti had better catalytic activity, reduced the poisoning effect of CaO to V5+, thus protecting the redox properties and increasing the surface acidic sites of the catalyst. Meanwhile, the in-situ DRIFTs results showed that the poisoning effect of CaO was weaker on the Ca-VWCu3P5Ti than that of the Ca-VWTi. In addition, the NH3 and NO species could be effectively adsorbed and activated on the surface of the Ca-VWCu3P5Ti by E-R mechanism. In this way, the harm of CaO to the vanadium-based catalysts was effectively reduced. This work provided a promising strategy to design vanadium-based catalysts with superior resistance to CaO in NH3-SCR reaction.