Objective To prepare tamsulosin hydrochloride sustained-release pellet by coating with acrylic copolymers. Methods EUDRAGIT^® NE 30 D was used as the main sustained-release material, EUDRAGIT^® L 30 D-55 and Methocel^® E3 were used as release adjust agent; a one layer sustained-release coating was done for tamsulosin hydrochloride-loaded pellet in bottom spray fluid bed. A three factor, three-level Box-Behnken design was used to optimize the percentages of EUDRAGIT^® L 30 D-55 and Methocel^® E3 in the total dry polymers and the weight gain of total dry polymers as the three nonlinear factors, which mainly influenced drug release of the pellets in the formula of sustained-release coating layer. In-vitro cumulative drug release after 2 h, 3 h and 5 h was tested and the following target range:2 h 12%-39%, 3 h 44%-70% and 5 h>70% were set for optimization. Results The formulation and process of one layer sustained-release coating, which was synergistically controlled by the three materials based on acrylic copolymers, was determined after optimization:the total dry polymers were applied with a weight gain of 12% on drug pellets, with EUDRAGIT^® L 30 D-55 dry polymers and Methocel^® E3 being 7% and 2% of the total dry polymers, respectively. The sustained-release pellets coated with the optimized formulation provided a release profile that was close to the predicted value and similar to that of the commercial product Harnal^® capsule pellets by f₂ similarity factor comparison (f₂ values of three batches were 71,73 and 80). Conclusion The established formulation and process is a simple and reproducible method to prepare tamsulosin hydrochloride sustained-release pellets with good stability.