The purpose of this study was to develop and optimize oral controlled-release formulations for tamsulosin hydrochloride using a combination of two cellulose ester derivatives, hydroxypropyl methylcellulose (HPMC) and hydroxypropyl methylcellulose phthalate (HPMCP), with Surelease as a coating material. A three-factor, three-level Box-Behnken design was used to prepare systematic model formulations, which were composed of three formulation variables, the content of HPMC (X(1)) and HPMCP (X(2)) and the coating level (X(3)), as independent variables. The response surface methodology (RSM) and multiple response optimization utilizing the polynomial equation were used to search for the optimal coating formulation with a specific release rate at different time intervals. The drug release percentages at 2, 3 and 5h were the target responses and were restricted to 15-30% (Y(1)), 50-65% (Y(2)) and 80-95% (Y(3)), respectively. The optimal coating formulation was achieved with 10% HPMC and 20% HPMCP at a coating level of 25%, and the observed responses coincided well with the predicted values from the RSM optimization technique. The drug release from pellets coated with the optimized formulation showed a controlled-release pattern (zero-order), in comparison with a commercial product (Harunal capsule). In conclusion, a novel, oral, controlled-release delivery system for tamsulosin hydrochloride was successfully developed by incorporating HPMC and HPMCP as coating additives into Surelease aqueous ethylcellulose dispersion.