Engineering the structure and/or composition of Pt nanoparticles has been an effective approach to improve the catalytic activity on a mass basis. Herein we demonstrate for the first time the synthesis of core-shell CdSe@Pt nanocomposites at different CdSe/Pt molar ratios. By reducing platinum precursors with sodium citrate in the presence of previously formed CdSe nanocrystals in aqueous phase, uniform core-shell CdSe@Pt nanocomposites are obtained as the dominant product. These core-shell CdSe@Pt nanocomposites exhibit superior catalytic activity toward reactions in direct methanol fuel cells (DMFCs). The inner-placed CdSe core is helpful for saving a substantial amount of valuable platinum metal. In addition, this core-shell structure also offers a vivid example for investigation of the lateral strain effect of the substrate on the deposited layers, and its influence on the catalytic activity of metal catalysts.