Recently, it has been reported that addition of a cosolvent significantly influences solubility of cellulose in ionic liquids (ILs), but little is known about the influence mechanism of the cosolvent on the molecular level. In this work, four kinds of typical molecular solvents (dimethyl sulfoxide (DMSO), N,N-dimethylformamide (DMF), CH3OH, and H2O) were used to investigate the effect of cosolvents on cellulose dissolution in C4mimCH3COO by molecular dynamics simulations and quantum chemistry calculations. It was found that dissolution of cellulose in IL/cosolvent systems is mainly determined by the hydrogen bond interactions between CH3COO− anions and the hydroxyl protons of cellulose. The effect of cosolvents on the solubility of cellulose is indirectly achieved by influencing such hydrogen bond interactions. The strong preferential solvation of CH3COO− by the protic solvents (CH3OH and H2O) can compete with the cellulose–CH3COO− interaction in the dissolution process, resulting in decreased cellulose solubility. On the other hand, the aprotic solvents (DMSO and DMF) can partially break down the ionic association of C4mimCH3COO by solvation of the cation and anion, but no preferential solvation was observed. The dissociated CH3COO− would readily interact with cellulose to improve the dissolution of cellulose. Furthermore, the effect of the aprotic solvent-to-IL molar ratio on the dissolution of cellulose in C4mimCH3COO/DMSO systems was investigated, and a possible mechanism is proposed. These simulation results provide insight into how a cosolvent affects the dissolution of cellulose in ILs and may motivate further experimental studies in related fields.