Traditional chemical treatments require high energy and concentrated agents to decrease high-lignin biomass recalcitrance during lignin removal. A low-cost and environment-friendly method via modifying the lignin structure without lignin degradation overcomes lignin barrier in wood-feeding termites. In this study, thermal hydroxyl radicals in the biomimetic system performed in high-lignin cassava stillage residues did not reduce total lignin level but altered the lignin monostructure. The major beta-0-4' remained conserved, whereas. hydroxylation and modification of selective intermonomer side-chain linkages occurred in the treated lignin. The treatment can enhance enzymatic saccharification with cellulose conversion of cassava stillage residues at 97%, twice higher than that of the control. In addition, the modified lignin exhibited low invalid adsorption capacity into commercial cellulases, thereby improving the performance of cellulosic feedstock. Modifying the lignin structure, instead of removing lignin, provides new insights for development of novel treatments for high lignin biomass.