In this study, we performed an extracellular proteomics and pair-wise TMT-labeling quantitative intracellular proteomics of SirexAA-E grown on glucose, xylose, xylobiose, or xylan-containing medium to gain a knowledge of extracellular and intracellular xylan responses of this bacterium. Moreover, the hemicellulose specific metabolic circuits in SirexAA-E were evaluated based on the interacellular proteomes, which has never been assessed in any Streptomycetes bacteria to the best of our knowledge.