AbstractIn the process of acid hydrolysis of cellulose, hydrolyzing the amorphous regions while retaining the crystalline regions is the key technology for obtaining microcrystalline cellulose products. This paper investigated the influence of FeCl3 on selective acid hydrolysis of crystalline regions and amorphous regions of cellulose. X-ray diffraction data indicated that FeCl3 can enhance the selectivity of acid hydrolysis for amorphous regions of cellulose, thus improving the crystallinity of hydrocellulose. Meanwhile, the crystalline structure did not change. Response surface methodology (RSM) was employed to optimize the crystallinity of hydrocellulose with respect to FeCl3 concentration, HCl concentration, reaction time, and temperature, and the relevant mathematical regression equation model was established. Under optimal conditions, the crystallinity of hydrocellulose was as high as 63.59% at 88.28 °C, 2.46 M HCl, 0.4 M FeCl3, and reaction duration of 64.02 min, which was in agreement with the predicted value.