NOx emission can be controlled through selective catalytic reduction (SCR) by ammonia in industry. However, the SCR catalysts are sensitive to contaminants. Searching for anti-poisoning catalysts has become a perpetual quest for large-scale SCR. Here, we report that hydrogenated titanium dioxide particles containing oxygen vacancies undergo in situ N-doping during NH3-SCR reaction. The N-doped hydrogenated TiO2−x exhibits high denitrification activity and selectivity, long-term stability, H2O and SO2 tolerance, and high poisoning resistance. The DRIFT spectra combined with density functional theory computations demonstrate that the N-dopant as the catalytic active site can enhance O2 and NO adsorption, which can be reduced by NH3via the Eley–Rideal mechanism. This is greatly different from traditional catalysts with metal active sites for NH3 adsorption. The high anti-poisoning performance can be ascribed to the weak interaction between N and toxic reactants. This discovery creates a new concept that non-metal active sites can replace conventional precious/transition metals to avoid poisoning, while being stabilized by in situ doping with reactants.