A good catalyst for efficiently controlling NOx emissions often demands strong resistance against alkali poisoning. Although the traditional ion-exchange model, based on acid-base reactions of alkalis with Brønsted acid sites, has been established over the past two decades, it is difficult to be used as a guideline to develop such an alkali-resistant catalyst. Here we establish a self-protection mechanism of deNOx catalysts against alkali poisoning by systematically studying the intrinsic nature of alkali resistance of V2O5/HWO (HWO = hexagonal WO3) that shows excellent resistance to alkali poisoning in selective catalytic reduction of NOx with NH3 (SCR). Synchrotron X-ray diffraction and absorption spectroscopies demonstrate that V2O5/HWO has spatially separated catalytically active sites (CASs) and alkali-trapping sites (ATSs). During the SCR process, ATSs spontaneously trap alkali ions such as K+, even if alkali ions initially block CASs, thus releasing CASs to realize the self-protection against alkali poisoning. X-ray photoelectron spectra coupled with theoretical calculations indicate that the electronic interaction between the alkali ions and ATSs with an energy saving is the driving force of the self-protection. This work provides a strategy to design alkali-resistant deNOx catalysts.