A simple, rapid, selective, sensitive, accurate and precise High Performance Liquid Chromatography (HPLC) with UV detection method has been developed and validated for determination of Tapentadol hydrochloride in human plasma. The chromatographic separation of Tapentadol hydrochloride was achieved with Chromasil C18 column using a mobile phase Methanol: water (60:40 v/v) at flow rate 1.0 ml/min. Plasma samples were processed using acetonitrile as precipitating agent to extract drug. The linearity for Tapentadol hydrochloride was found to be 100-1000 ng/ml with regression coefficient (r2) 0.9980. The limit of quantification in plasma for Tapentadol hydrochloride was found to be 100 ng/ml. The mean recovery was obtained at 85.20 %. The method has been used to perform pharmacokinetic and bioequivalence studies in human plasma.