Addition of non-ionic surfactants (NIS) is known to accelerate enzymatic lignocellulose hydrolysis. The mechanism behind this accelerating effect is still not elucidated but has been hypothesized to originate from favorable NIS–lignin interactions which alleviate non-productive adsorption of cellulases to lignin. In the current work we address this hypothesis using tannic acid (TAN) as a general poly-phenolic model compound (for lignin and soluble phenolics) and measure the mutual interactions of cellulases (CBHI, CBHII, EGI, EGII and BG), TAN and NIS (Triton X-100) using isothermal titration calorimetry (ITC). The experimental results suggest rather strong enzyme-specific interactions with TAN in reasonable agreement with enzyme specific lignin inhibition found in the literature. Enzyme–TAN interactions were disrupted by the presence of NIS by a mechanism of strong TAN–NIS interaction. The presence of NIS also alleviated the inhibitory effect of TAN on cellulase activity. All together the current work provides strong indications that favorable NIS–poly-phenol interactions alleviate non-productive cellulase–poly-phenol interactions and hence may provide a mechanism for the accelerating effect of NIS on lignocellulose hydrolysis.