The objective of this work was to further elucidate the dissolution process of acetaminophen crystals at the molecular level. The differences in the etching patterns from different solvents were used to study the interactions between solvent and acetaminophen molecules at the solid-liquid interface, such as solubilizing ability and potential solvent adsorption. The predicted etching patterns, based on the projections of attachment energies on the corresponding faces together with the solubilizing ability of the solvents, fit the observed etching patterns well. On the (001) face, the etching patterns were predominantly in the direction of the a-axis, which was also the direction of the dominant attachment energy. On the (110) face, the etching patterns were consistently in the direction of the c-axis irrespective of solvent used, and they were variable in other directions. These were well fit by the predicted etching patterns accounting for the different solubilizing ability of solvents. Both the most significant etching pattern deviations (on the (010) face) and the most significant morphology changes were observed with dichloroethane for acetaminophen. The morphology of acetaminophen crystals from different solvents showed that only the crystals from dichloroethane had significant elongation along the c-axis, which suggests the existence of stronger adsorption in the a-axis and b-axis directions than along the c-axis for dichloroethane. Overall, the current work suggests that the crystal interaction network, together with the interactions between solvent and acetaminophen, affects surface diffusion and plays an important role in the dissolution process.