The crystal structure of tetracycline hydrochloride was simulated by Bravais-Friedel-Donnay-Harker (BFDH) and modified attachment energy (AE) models, based on the single-crystal data obtained by Material Studio software. A comparison to the scanning electron microscopy image of tetracycline hydrochloride indicated that the AE model was superior to the BFDH model. The morphology predicted by the AE model was further improved by taking account of the interaction effect between the growing faces and the solvent molecules. The final modification of the AE prediction provided good accordance with the observed results of the experiments.