Simple, accurate and precise and economical UV–spectroscopy method have been developed and validated for the estimation of Tadalafil and Fluoxetine HCl in a synthetic mixture. Tadalafil is used in treatment of Erectile Dysfunction and Fluoxetine HCl is used in depression. The Tadalafil and Fluoxetine HCl stock solutions are prepared in methanol solution. At zero crossing point (ZCP) of Tadalafil (230nm) Fluoxetine HCl showed a measurable derivative absorbance, whereas at zero crossing point (ZCP) of Fluoxetine HCl (235nm) Tadalafil showed a appreciable derivative absorbance value. The Tadalafil and Fluoxetine HCl are linear in concentration range of 5-25 μg/ml. Developed method was validated according to the ICH Q2 (R1) guidelines. The precision were found within limits (RSD< 2%). Accuracy were determined by recovery studies and showed % recovery between 97 to 100 % for both the drugs Tadalafil and Fluoxetine HCl. The LOD and LOQ values of Tadalafil at ZCP 230 nm were found to be 0.24 and 0.74 correspondingly and for Fluoxetine HCl at ZCP235nm were found to be 0.29 and 0.89 correspondingly.