A novel strategy to synthesize a size-selective catalyst consisting of a Pd-containing silica core and an outer silica shell with controllable pore size, was developed. Such intended structures were confirmed with N2 sorption, XRD, TEM and SEM. The pore sizes on the shell could be further tailored through silylation with organosilanes with variable chain lengths. This intriguing nanostructured catalyst showed a high activity in the aerobic oxidation of alcohols. Impressively, when the pores on the shell were tailored to particular sizes the catalyst exhibited size-selective catalysis, and the substrate molecules with only a slight difference in molecular size could be discriminated. This study potentially supplies a new approach for constructing size-selective catalysts.