AbstractA previous study reported that a novel Aspergillus oryzae strain (CGMCC5992) can synthesize lignin hydrolytic enzymes for lignin degradation from straw. The present work involves the different gene expression of A. oryzae 5992 grown in media using lignin and glucose as carbon sources by suppression subtractive hybridization. Surprisingly, peroxidase was found in up-regulation genes, which is the key enzyme for degrading lignin. This shows that A. oryzae 5992 can secrete peroxidase in the presence of lignin. The functions of up-regulation genes also included gluconeogenesis, repairs, as well as signal and transporter proteins in the cell membrane. In addition, the down-regulation of genes was closely related to the aerobic metabolism of glucose, the fatty acid synthesis of the cell membrane, and the synthesis and utilization of ATP. Therefore, A. oryzae could regulate metabolism using lignin as carbon source, including lignin degradation promotion, glucose metabolism inhibition, and glucose regeneration.