Vanadium phosphorus oxide (VPO) catalysts are the only industrial catalyst for the selective oxidation of n-butane. Doping with metal additives and modulation with organic additives are effective means to improve the performance of VPO catalysts. In this work, the simultaneous organo-metallic modification was achieved by adding magnesium chloride-alcohols deep eutectic solvents (MgCl2/alcohol) during the synthesis of VPO catalyst precursors. The VPO precursors and catalysts were analyzed by scanning electron microscope (SEM), BET automatic specific surface and porosity analyzer (BET), X-ray diffractometer (XRD), Fourier transform infrared spectrometer (FT-IR), Raman spectrometer (Raman) and X-ray photoelectron spectroscopy (XPS), et al. The effect of deep eutectic solvents with different hydrogen bond donors about ethylene glycol (EG), 1-4 butanediol (BDO), and glycerol (GL) on VPO catalysts was investigated. The microscopic morphology, specific surface area, physical phase, surface properties, and crystalline phase transition temperature of VPO precursors as well as catalysts were analyzed in detail. The performance of VPO catalysts was evaluated in the fixed bed reactor for n-butane oxidation selectivity to maleic anhydride. The results showed that the introduction of deep eutectic solvent MgCl2/EG in the synthesis of VPO catalyst precursors can modulate the morphology and crystalline phase composition, thus improving the catalyst performance. The use of MgCl2/EG to modulate the preparation of VPO precursors can obtain catalysts with better dispersion, larger specific surface area, the highest total acid, and a number of active surfaces. VPO-MgCl2/EG catalysts had good dispersion, large specific surface area, a high number of active surfaces (020), enrichment of surface P atoms, and low average valence state of surface V. Furthermore, (VO)2P2O7 and VOPO4 crystalline phases synergistically improved the performance of VPO-MgCl2/EG catalysts. In conclusion, VPO-MgCl2/EG exhibited excellent catalytic performance in the reaction of n-butane oxidation selectivity to maleic anhydride, which provides a new idea for the preparation of VPO catalysts.