Laccase is one of the most important oxidoreductase with industrialization potential. However, due to the high cost and catalytic toxicity of laccase synthetic mediator, the laccase-mediator-system still cannot achieve industrialization. Therefore, searching for high efficient, environment-friendly, and cheap natural mediator from small molecule precursors or intermediates and degradation products of lignin has been considered as a hot research topic. Therefore, we introduce the type and catalytic mechanism of laccase mediator, the composition and separation of natural laccase mediator from water washed solution of steam exploded straw, black liquor and lignocelluloses degradation products during the fermentation of white-rot fungi. We also provide the theoretical and technical direction for exploring of high reactive of laccase natural mediators and achieving the oriented high-value utilization of lignocellulose degradation products.