A Simple and precise RP-HPLC method has been developed and validated for the estimation of Duloxetine hydrochloride (DLX) in bulk and pharmaceutical dosage forms. Chromatography is carried out on an inertsil column (250×4.6, 5 μm) using a mobile phase containing 0.02% formic acid: acetonitrile (72:28% v/v) at a flow rate of 1 ml/min. The analyte was monitored using UV detector at 230 nm. The retention time is found to be 5.243 min for Duloxetine hydrochloride. The proposed method was found to be linear in the concentration range of 2-10 μg/ml with a correlation coefficient of 0.999. The mean recoveries obtained for Duloxetine hydrochloride were in the range of 98.77-102.05%. The limit of detection (LOD) and limit of quantification (LOQ) were found to be 0.0206 and 0.062 μg/ml respectively. The developed method has been statistically validated according to ICH guidelines and found to be LC-MS compatible, simple, precise, and accurate with the prescribed values. Thus the proposed method was successfully applied for the estimation of Duloxetine hydrochloride in routine quality control analysis in bulk and formulations.