Valorization of cellulose through tandem chemical conversions depends significantly on the controllable depolymerization of cellulose to poly-/oligo-/monosaccharides with the desired rate and degree. Herein, we report the controlled depolymerization of high-loading cellulose (15.0 wt %) into polysaccharides with a uniform polymerization degree of 38−48 by cetyltrimethylammonium bromide (CTAB) in water and its underlying mechanisms. We found that CTAB was adsorbed on the cellulosic surface via hydrophobic interaction, thereby acting as an "adhesive" for reducing the interfacial tension between H 2 O/ H 3 O + and the cellulosic surface, helping in swelling of the crystalline region, promoting depolymerization of the amorphous region, and inhibiting repolymerization of polysaccharides. Further kinetic study demonstrated an increment of ∼400 times in the preexponential factor (10 19.3 vs 10 16.7 min −1 ), 19.6 kJ•mol −1 in activation energy (181.5 vs 161.9 kJ•mol −1 ), and 3.5 times in rate constant for the CTAB-promoted depolymerization, which highlighted the offsetting of the elevated reaction energy barrier by boosting the collision frequency between H 2 O/H 3 O + and cellulose. Furthermore, we illustrated the synergistic role of 1,4-dioxane on this controllable depolymerization by lowering the activation energy to 143.7 kJ•mol −1 for reducing polysaccharide accumulation at the cellulosic interface. This in-depth understanding is of great significance for the sustainable transformation and utilization of cellulose in future biorefineries.