Understanding the interactions between solvent molecules and cellulose at a molecular level is still not fully achieved in cellulose/N,N-dimethylacetamide (DMAc)/LiCl system. In this paper, cellobiose was used as the model compound of cellulose to investigate the interactions in cellulose/DMAc/LiCl solution by using Fourier transform infrared spectroscopy (FTIR), (13)C, (35)Cl, and (7)Li nuclear magnetic resonance (NMR) spectroscopy and conductivity measurements. It was found that when cellulose is dissolved in DMAc/LiCl cosolvent system, the hydroxyl protons of cellulose form strong hydrogen bonds with the Cl(-), during which the intermolecular hydrogen bonding networks of cellulose is broken with simultaneous splitting of the Li(+)-Cl(-) ion pairs. Simultaneously, the Li(+) cations are further solvated by free DMAc molecules, which accompany the hydrogen-bonded Cl(-) to meet electric balance. Thereafter, the cellulose chains are dispersed in molecular level in the solvent system to form homogeneous solution. This work clarifies the interactions in the cellulose/DMAc/LiCl solution at molecular level and the dissolution mechanism of cellulose in DMAc/LiCl, which is important for understanding the principle for selecting and designing new cellulose solvent systems.