Understanding the evolution of surface morphology or surface texture of molecular crystals by dissolution/etching may be useful in determining the dissolution mechanisms at the molecular level. In this study, partial dissolution tests were conducted on the (010) face of acetaminophen single crystals with selected solvents: water, dichloroethane, pyridine, acetone, ethyl acetate, and acetic anhydride. Surface textures and etching patterns were examined with an atomic force microscope (AFM). It was found that etching patterns were regular and their shape depended on the solvent used for the etching. The etching patterns observed were parallelogram(by water and acetic anhydride), slit (by dichloroethane), hexagonal (by pyridine), square (by acetone), or rectangular (by ethyl acetate). It seems that all etching patterns are related to the underlying crystal structure. The crystal structure was used in simulation of the dissolution process by a computer model. Two essential events were considered during the simulation, detachment of crystal molecules, and surface diffusion of the desorbed molecules. Simulation results indicated that surface diffusion played the key role in forming etching patterns. The surface diffusion was thought to be guided or confined by the underlying crystal structure,especially the supramolecular interaction network. The discrepancy in the etching patterns between the simulation results and some of the experimental observations was explained by adsorption of solvent molecules on the crystal surface. It was likely that the adsorption of solvent molecules changed or interrupted the: original interaction network within the crystal structure, leading to the mutation of the etching pattern. Our study indicated that the etching pattern at the crystal surface was influenced not only by the solvent-solid interaction but also by the crystal structure and the mutual recognition between solvent molecules and crystal molecules.