Vermiculite is a natural, environmentally friendly mineral, which is widely used in construction, thermal insulation, metallurgy, and agriculture. In this study, vermiculite and acid-activated vermiculite was used as a solid acid catalyst for the hydrolysis of cellulose in water. The vermiculite based solids were characterized by XRD, FT-IR, and BET. The effects of reaction time, reaction temperature, mass ratio and water amount on the reaction were also investigated in the batch reactor. The results showed that the highest total reducing sugars (TRS) yield of 40.1% could be obtained on the vermiculite activated by 35(wt)% H2SO4 with the mass ratio of catalyst to cellulose of 0.18 and water to cellulose of 16 at 478 K for 3.5 h. The acid-activated vermiculite was also a stable catalyst through calcination at 628 K and the yield of TRS decreased from 40.1% to 36.2% after three times reuse. The results showed that the crystal structure of vermiculite was almost destroyed and the surface -OH groups increased after the acid treatment. However, the synergistic effect of strongly electrostatic polarization and Brönsted acid was responsible for the efficient conversion of cellulose. Finally, the mechanism of cellulose hydrolysis on the acid-activated vermiculite was suggested. This work provides a promising strategy to design an efficient solid catalyst for the cellulose hydrolysis, and also expands the use of vermiculite in a new field.