A new HPLC method was developed for selective and simultaneous determination of Guaifensen and Dextromethorphan HBr tablets 1200/60 mg. The chromatographic separation was achieved on a Acquity UPLC BEH, C18,100 x 2.1 mm, 1.7um column. The mobile phase consisted of buffer, acetonitrile and methanol delivered at a flow rate of 0.15 ml/min and dual wavelength at 271 nm for Guaifensin and 220 nm for Dextromethorphan with UV detector. Accuracy found by % recovery from 98.2 to 102.2 at 50 to 150% level and the linearity results for Guaifensen and Dextromethorphan HBr in the specified concentration calibration curves linear with coefficient of variation not less than 0.99. The proposed was found to be specificity, linearity, and precision, Intermediate precision and accuracy, stability of analytical solution and robustness. The validation was performed according to the ICH guide lines.