Regulating the geometric and electronic configurations of interfacial active sites is an attractive approach to design high-efficiency catalysts. Here, guiding by the electronic metal–support interaction (EMSI), we constructed the chemical state-tunable nanoparticulate Ru on three-dimensional (3D) porous TiO2 nanoflowers derived from 2D Ti3C2 MXene nanosheets (Ru/TMTFs-x). Benefitting by the unique geometric architecture and EMSI-directed electron-deficient configuration of Ru, the catalysts are efficient in benzene semi-hydrogenation, achieving a high turnover frequency (TOF, 7.2 s−1) and an excellent initial cyclohexene selectivity (78%) on the most electron-deficient Ru/TMTFs-773 catalyst. Despite that the TOFs are nearly identical along with the enhancement in electron-deficient degree of Ru on Ru/TMTFs-x by tuning the Ti4+: Ti3+ molar ratios, which was originated from the resemblances in Ru size and acidity, a positive correlation between cyclohexene selectivity and electron-deficient degree of Ru was recognized. By virtue of kinetics analyses and density functional theory (DFT) calculations, the promotion in net generation rate of cyclohexene and the weakening in cyclohexene adsorption on Ru/TMTFs-x when lowering the electron density of Ru are responsible for the selectivity enhancement. A linearity between selectivity and the percentage of Ti4+ sites was identified, further corroborating the EMSI-mediated selectivity enhancement on Ru/TMTFs-x.