Combined experimental and computational studies show that, upon reducing the diameter of Pt nanoparticles down to 1 nm, a collapse in the crystalline structure occurs spontaneously and the thus-induced quantum size effect causes a decline in the catalytic activity toward hydrogen oxidation reaction (HOR). The conversion from crystalline to amorphous structure is rationalized by molecular dynamic simulations; and the special electronic structure of amorphous Pt nanoparticles is revealed via density functional calculations. Not only has the present work estimated the Pt utilization limit for HOR, but it also expands the structure-activity relationship of Pt nanoparticles toward HOR to an extent that has rarely been touched.