By applying fumed SiO2 and the deposition–precipitation method based on organic medium, the composite VPO/fumed SiO2 catalysts were first prepared and tried for partial oxidation of n-butane to maleic anhydride. In the temperature range of 653–693 K the fumed SiO2-based catalysts not only showed good activity but also maintained sufficiently high MA selectivity in comparison to some conventional supported VPO catalysts. As an example, the catalyst with 30% VPO content showed butane conversion of 60% and MA selectivity of 58 mol% at 673 K. The turnover rates of low loading samples are found to be higher than that of high loading sample as well as unsupported catalyst. Besides the unique interaction which may exist between VPO component and the fumed SiO2 material, co-existence of dominant (VO)2P2O7 and minor VOPO4 in these non-equilibrated catalysts may be favorable for MA formation. Moreover, introducing the additive of polyethylene glycol (PEG) in the preparation medium can obviously enhance the dispersion of VPO component and hence lead to a more selective catalyst.