Abstract: OBJECTIVE To prepare Paroxetine Hydrochloride Extended-release tablets by hydrophilic gel-forming matrix materials and assess the quality. METHODS Combined with two types of hydrophilic gel-forming matrix material of HPMC K100LV and HPMC K4M to prepare Paroxetine Hydrochloride Extended-release tablets. Paroxetine Hydrochloride Extended-release tablets were manufactured by the dry granulation process and then coated with enteric coating suspension. The formulations were optimized by orthogonal experiment design utilizing dissolution similarity f₂ as an evaluation index. The drug content and impurity were analyzed by HPLC. The stability study was conducted under accelerated and long term conditions. RESULTS The optimized formulation of Paroxetine Hydrochloride Extended-release tablets showed acceptable quality and stability and similar dissolution profiles with the brand product. CONCLUSION This method to prepare Paroxetine Hydrochloride Extended-release tablets is feasible.