Diclofenac sodium (DIC) and Diflunisal (DIF) are two widely used analgesic drugs formulated in combined dosage form to treat inflammation and relive pain in many conditions. In this work, four accurate, precise and specific spectrophotometric and chromatographic methods have been developed and validated for determination of these drugs in their bulk powder and pharmaceutical dosage form. The developed methods are Q-analysis[ graphical absorbance ratio method] (Method I), dual wavelength (Method II), mean centering of ratio spectra MCR (Method III) and TLC-Denitometric (Method IV), In method (I) the absorbance values at 268nm (λ iso) and 226.6 nm (λ max of DIF) were used for computing the Q analysis equations from which concentrations of DIC and DIF have been obtained. In method (II) two wavelengths were selected for each drug in such a way that the difference in absorbance was zero for the second one. The wavelengths 253.6 and 308.6 nm were used for measuring DIC while 287 and 308.6 were used for DIF. In method (III) absorption spectra of each drug were recorded, divided by suitable divisor and the obtained ratio spectra were then mean centered. Method (IV) is TLC –Densitometric method that depends on quantitative separation of DIF and DIC on TLC plates using hexane: ethylacetate: acetic acid (5:4.8:0.2, by volume) as mobile phase and scanning at 280 nm The developed methods were validated according to ICH guidelines demonstrating good accuracy and precision. The results were statistically compared with those obtained by reported method and no significant difference were found between them.