Propylsulfonic acid functionalized SiO2 core/alkyl- or phenyl-bridged organosilica shell structured PrSO3H-SiO2@Si(R)Si (R = -C2H4-, -C6H4- or -C6H4-C6H4-) nanospheres are facilely prepared by a CTAB-directed one-pot two-step condensation strategy. The morphological characteristics, textural properties, Bronsted acid nature and structure of the PrSO3H-SiO2@Si(R)Si nanospheres are well characterized. The materials are successfully applied in the catalytic transformation of D-fructose into the important organic chemical, ethyl levulinate, in the presence of ethanol as both reactant and solvent. The catalytic activity of the PrSO3H-SiO2@Si(R)Si nanospheres outperform commercially available Amberlyst-15, HY zeolite and HCl, mainly attributing to their strong Bronsted acid nature; additionally, unique core-shell structure with excellent porosity properties and well adjusted hydrophilicity/hydrophobicity also give the positive influence on the ethanolysis activity, which can improve the accessibility of the reactants to the PrSO3H sites and facilitate the multi-step ethanolysis reaction proceeding to the formation of the final product. The PrSO3H-SiO2@Si(R)Si nanospheres can be reused three times without obvious activity loss, contributed from covalent bonding of the PrSO3H groups with the silica and organosilica framework as well as hydrophobic PrSO3H-functionalized organosilica shell.