Abstract: Lignocellulosic is one of the most difficult degradable substances during organic composting process. Enhancing degradation of lignocellulosic is beneficial to promote the rapid decomposition of compost and improve the quality of compost. An experiment was conducted to study the effects of original zymolytic condition of brewer's spent grains-based bio-organic fertilizer on degradation of total carbon and lignocellulosic by using the quadratic uniform-precision rotatable central composite design including four factors and five levels. The results show that the influence of ratios of straw to lees is important for the degradation of total carbon and hemicellulose, and the influence of water content is important for the degradation of cellulose and lignin. The best conditions for the degradations are that pH value is 6.63-7.02, inoculation fungal biomass is 0.49%-0.551%, water content is 65.52%-66.68%, and ratios of straw to lees is 41.61%-44.32%.