Background: Berberine hydrochloride (BH) is widely used as a nonprescription drug to treat diarrhea without drug resistance and side effects worldwide. However, its drastic bitterness affects patient compliance severely. Hence, it is essential to mask the bitter taste of BH. Objective: Powder surface modification technology is attempted to mask the bitterness of BH through changing the surface properties in vibromill. The purpose of this study was to apply this technology to mask the bitterness of BH and improve the patient compliance. Materials and Methods: Initially, to prepare the modifier-BH composites, some parameters were optimized, including type of modifiers, ratio between BH and modifiers, and composite time. Then, the contact angles, scanning electron microscopy, and infrared (IR) spectroscopy were utilized to evaluate the microstructure of composites. Moreover, electronic tongue measurement, animal performance test, and bitterness evaluation methods were applied to evaluate the masking effect. Results: Based on the results of bitter taste evaluations, mannitol was chosen as the best modifier, and the optimal ratio of BH and mannitol was 6:4 with grinding together for 2 min in vibromill. For the composites prepared by this process, the IR spectroscopy and surface properties were similar with that of mannitol, and the microstructure was also demonstrated that small particles of mannitol successfully coated on the surface of BH. Special structure of the composites decreased the contact area between BH and external media and finally inhibited the bitterness. This effect was confirmed by three different kinds of methods. Conclusion: Our study provides a novel method to mask the bitter taste of drugs. It will be of great interest to pharmaceutical experts and pharmacists.