Fabrication of sufficient oxygen vacancies and exposure of active sites to reactants are two key factors to obtain high catalytic activity in the water-gas shift (WGS) reaction. However, these two factors are hard to satisfy spontaneously, since the formation of oxygen vacancies and encapsulation of metal nanoparticles are two inherent properties in reducible metal oxide supported catalysts due to the strong metal-support interaction (SMSI) effect. In this work, we find that addition of alkali to an anatase supported Ni catalyst (Ni/TiO2(A)) could well regulate the SMSI to achieve both more oxygen vacancies and depression of encapsulation; therefore, more than 20-fold enhancement in activity is obtained. It is found that the in situ formed titanate species on the catalyst surface is crucial to the formation of oxygen vacancies and depression of encapsulation. Furthermore, the methanation, a common side reaction of the WGS reaction, is successfully suppressed in the whole catalytic process.