(La,Sr)TiO3 has been investigated as a promising anode material for solid oxide fuel cells (SOFCs) owing to its high electronic conductivity and superior phase stability. However, the low catalytic activity of (La,Sr)TiO3 materials is a major obstacle to the application of SOFCs. Exsolution has emerged as an effective strategy to overcome the low catalytic activity of (La,Sr)TiO3 materials. In this work, Ni-doped A-site-deficient La0.4Sr0.4TiO3-δ (LST) (i.e., La0.4Sr0.4Ti0.94Ni0.06O3-δ; LSTN) with in-situ exsolved Ni nanoparticles (NPs) was developed and the effects of exsolved Ni NPs on H2 oxidation was investigated. The doped Ni was exsolved and formed NPs on the LSTN surface under reducing conditions. Owing to the high catalytic activity of the exsolved Ni NPs, the SOFC with LSTN-Ce0.9Gd0.1O2-δ (GDC) yielded a maximum power density of 0.46 W cm−2 at 850°C, 91% higher than that of the cell with LST-GDC, as well as high long-term and redox stability. Furthermore, density functional theory calculations revealed that the adsorption and dissociation of H2 were more favorable for exsolved Ni NPs than for pure Ni owing to the more positively charged surface of the exsolved Ni NPs in the LSTN. These results demonstrated that exsolution is an effective method for improving the electrocatalytic activity of perovskite (La,Sr)TiO3 materials.