Al-MCM-41 material was adopted for comparison with amorphous large-pore silica, as the support material for vanadium-phosphorus-oxide (VPO) specimen. The support effects on the physico-chemical characteristics and the catalytic behavior of the supported VPO catalysts in the selective oxidation of n-butane were investigated. The results revealed that due to the difference in nature of the support and the variation in VPO loading, the physico-chemical properties of the supported samples, namely, the surface area, the pore size distribution and the structural features of the supported VPO component, etc. changed notably. This in turn influenced the catalytic performance of the supported VPO specimen. Compared with the large-pore silica-supported VPO, the Al-MCM-41-supported VPO catalyst exhibited a notable enhancement in maleic anhydride (MA) selectivity and a slight decrease in n-butane conversion, largely due to the unique interaction involved between the VPO component and the Al-MCM-41 support. Butane conversion increased with increasing vanadium loading, accompanying a remarkable decrease in the MA selectivity, originating likely from the increased number of the reaction sites that are more reactive but less selective in nature. From a comparison of sample preparations, it was found that the precipitation in organic medium showed superiority to the acidic aqueous impregnation in preparing the MCM-41-supported VPO species, and that the unique structure of MCM-41 did play an important role in determining the physico-chemical properties of the supported VPO specimen.