The aim of this study was to explore the catalytic performance of the oxidative depolymerization of enzymatic hydrolysis lignin from cellulosic ethanol fermentation residue by different vanadium substituted Keggin-type polyoxometalates (K5[SiVW11O40], K6[SiV2W10O40], and K6H[SiV3W9O40]). Depolymerized products were analyzed by gel permeation chromatography (GPC), gas chromatography–mass spectrometer (GC/MS), and two-dimensional heteronuclear single quantum coherence nuclear magnetic resonance (2D HSQC NMR) analysis. All catalysts showed an effective catalytic activity. The best result, concerning the lignin conversion and lignin oil production, was obtained by K6[SiV2W10O40], and the highest yield of oxidative depolymerization products of 53 wt % was achieved and the main products were monomer aromatic compounds. The HSQC demonstrated that the catalysts were very effective in breaking the β-O-4 structure, the dominant linkage in lignin, and the GPC analysis demonstrated that the molecular of lignin was declined significantly. These results demonstrate the vanadium substituted silicotungstic polyoxometalates were of highly active and stable catalysts for lignin conversion, and this strategy has the potential to be applicable for production of value-added chemicals from biorefinery lignin.