Background: Derivative spectroscopy provides a greater selectivity and spectral discrimination than common spectroscopy. It is the dominant approach for resolution of one analyte whose peak is hidden by a large overlapping peak of another analyte in multi component analysis. Hence, this technique we have been successfully applied for simultaneous quantification of lornoxicam and paracetamol in combined tablets. Materials and Methods: The method is based on the derivative spectrophotometric method at zero-crossing wavelengths. Two wavelengths 347 nm (zero crossing point for paracetamol) and 272.5nm (zero crossing point for lornoxicam) were selected for the quantification of lornoxicam and paracetamol respectively, using 0.01 M sodium hydroxide as solvent and Shimadzu (Japan) UV-Visible spectrophotometer (UV-1800) instrument. Results: The first derivative amplitude-concentration plots were rectilinear over the range of 2-22 μg/mL and 1-75 μg/mL with detection limits of 0.06 and 0.08 μg/mL and quantification limits of 0.2 and 0.26 μg/mL for lornoxicam and paracetamol respectively. The proposed method was statistically validated as per ICH guidelines. The percentage recovery was within the range between 97-101 and % relative standard deviation for precision and accuracy of the method was found to be less than 2. Conclusion: The proposed method was effectively applied to routine quality control analysis of studied drugs in their tablet formulations.