OBJECTIVE： To optimize the formulation of Phencynonate hydrochloride transdermal patch. METHODS： Phencynonate hydrochloride transdermal patch was prepared by solvent evaporation method. Using 48 h accumulative transdermal volume as index， single factor test and Box-Behnken design-response surface methodology were used to optimize drug dosage， the amount of transdermal enhancers azone and pressure-sensitive adhesive， and evaluate the appearance， adhesion of the formulation prepared by the best prescription. RESULTS： The optimized formulation was as follows as 263 mg drug dosage， 165 mg azone， 1.94 g pressure-sensitive adhesive and 1.6 g methanol. 48 h accumulative transdermal volume of prepared patch was （119.48±2.95） μg/cm2（n＝5）， related error of which to predicted value was 2.48％. The prepared patch showed smooth surface and incision， good adhesiveness. CONCLUSIONS： Phencynonate hydrochloride transdermal patch is prepared successfully， its accumulative transdermal volume is in agreement with predicted standard.