OBJECTIVE： To prepare Venlafaxine hydrochloride sustained-release tablets， and to investigate the characteristics of drug release. METHODS： Using glyceryl behenate as lipidic matrix material and HPMC as hydrophilic matrix material， the kind and dosage of excipients were screened by single factor experiment. Using 4， 8， 24 h accumulative release rate and the deviation summation of ideal values as index， the viscosity of HPMC， the amounts of HPMC K15M and glyceryl behenate were optimized by orthogonal test. The dissolution curves were fitted by different equations. RESULTS： The optimal formulation was as follows as venlafaxine hydrochloride 8.5 kg， HPMC K15M 15 kg， glyceryl behenate 26 kg， magnesium stearate 0.5 kg. 4， 8， 24 h accumulative release rates of prepared matrix sustained-release tablets were 34.3％， 63.9％ and 99.2％， respectively. The releases profiles of hydrophilic and lipidic matrix sustained release tablets followed first-order equation in vitro mainly through matrix erosion. CONCLUSIONS： Venlafaxine hydrochloride hydrophilic and lipidic matrix sustained-release tablets with good sustained-release effect have been prepared successfully.