A zirconium-doped mesoporous silica with MCM-41-type structure has been used as a support for nickel oxide and tested in the selective catalytic reduction (SCR) of NO with ammonia. From XPS and H2-TPR data, two kinds of catalysts can be prepared, depending on the nickel loading. Thus, low nickel loadings (1 and 3 wt%) give rise to small particles located in mesopores, whereas higher nickel contents (6 and 12 wt%) favour the formation of larger nickel oxide particles, mainly situated on the external surface. Moreover, the small particles are less reducible, owing to their strong interaction with the internal surfaces of the support. The catalyst with a nickel loading of 6 wt% is very active in the SCR of NO with NH3 at 400 °C, leading to an NO conversion of close to 60%, with a selectivity towards N2 close to 100% and formation of a negligible amount of N2O. From the experimental data, a correlation between reducibility and catalytic activity can be established.