ABSTRACTA hybrid molecular mechanics–molecular dynamics simulation method has been performed to study the effects of moisture content on the mechanical properties of microcrystalline cellulose (MCC) and the mobility of the water molecules. The specific volume and diffusion coefficient of the water increase with increasing moisture content in the range studied of 1.8–25.5 w/w%, while the Young's modulus decreases. The simulation results are in close agreement with the published experimental data. Both the bound scission and free‐volume mechanisms contribute to the plasticization of MCC by water. The Voronoi volume increases with increasing moisture content. It is related to the free volume and the increase enhances the mobility of the water molecules and thus increases the coefficient of diffusion of the water. Moreover, with increasing moisture content, the hydrogen bonding per water molecule between MCC–water molecules decreases, thus increasing the water mobility and number of free water molecules. © 2019 The Authors. Journal of Polymer Science Part B: Polymer Physics published by Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2019, 57, 454–464