The influence of metal particle size over heterogeneous catalysts on the catalytic performance has always been an interesting subject due to its significance from both fundamental and practical perspectives. In this work, we regulated the synthesis of TiO2 by the hydrolysis of different titanium precursors, and as-prepared TiO2 supports were employed to load Ru with impregnation method. Interestingly, we synthesized three Ru-TiO2 catalysts with different Ru particle sizes of 1.1, 2.9 and 5.2 nm. The Ru-TiO2 catalysts were next tested for CO2 hydrogenation reaction, the results show that the medium Ru particles on TiO2 exhibited the best CO2 methanation activity. Based on the characterizations, we observed that the medium Ru particles exhibited the best redox properties compared with small and large Ru particles, which was beneficial to the H2 dissociation; in addition, the medium Ru particles exhibited a moderate ability to activate CO2, resulting in the most favorable formation and decomposition of bidentate bicarbonate. Consequently, the Ru-TiO2 catalyst with medium Ru particles showed the highest activity for CO2 methanation. This study provides a new method to prepare Ru-TiO2 catalysts with different Ru sizes and also presents an understanding of Ru particle size effects on CO2 hydrogenation.