AbstractConsiderable attention has been drawn to tune the geometric and electronic structure of interfacial catalysts via modulating strong metal-support interactions (SMSI). Herein, we report the construction of a series of TiO_2−x/Ni catalysts, where disordered TiO_2−x overlayers immobilized onto the surface of Ni nanoparticles (~20 nm) are successfully engineered with SMSI effect. The optimal TiO_2−x/Ni catalyst shows a CO conversion of ~19.8% in Fischer–Tropsch synthesis (FTS) process under atmospheric pressure at 220 °C. More importantly, ~64.6% of the product is C₂₊ paraffins, which is in sharp contrast to the result of the conventional Ni catalyst with the main product being methane. A combination study of advanced electron microscopy, multiple in-situ spectroscopic characterizations, and density functional theory calculations indicates the presence of Ni^δ−/TiO_2−x interfacial sites, which could bind carbon atom strongly, inhibit methane formation and facilitate the C-C chain propagation, lead to the production of C₂₊ hydrocarbon on Ni surface.