The aim of the present study was to screen the effects of the formulation variables - POLYOX molecular weight (X1), the ratio of POLYOX/Avicel PH102 (X2) and the amount of POLYOX and Avicel PH102 (X3), hardness (X4), HPMCP amount (X5), Eudragit L100 amount (X6), and citric acid amount (X7) - on the paroxetine hydrochloride release from POLYOX matrix tablet using the Plackett-Burman screening design. Paroxetine hydrochloride matrix tablets were prepared according to a 7-factor-12-run statistical model and subjected to a 8-h dissolution study in Tris buffer at pH 7.5. The regression results showed that POLYOX molecular weight (X1) and POLYOX/Avicel PH102 ratio (X2) had significantly influence on the drug release mechanism and drug release rate as main effects. Hardness (X4) had an insignificant effect on the drug release mechanism but a significant effect on the drug release rate. On the other hand, HPMCP, Eudragit L100 and citric acid had an insignificant effect on the both responses. The information obtained by screening design study can be expected to be useful for further formulation studies.