Asimple,novelandsensitivespectrophotometricmethodwasdescribedforsimultaneousdetermination ofmercuryandpalladium.Themethodisbasedonthecomplexformationofmercuryandpalladiumwith Thio-Michler’sKetone(TMK)atpH3.5.Allfactorsaffectingonthesensitivitywereoptimizedandthelineardynamicrangefordeterminationofmercuryandpalladiumfound.Thesimultaneousdeterminationof mercuryandpalladiummixturesbyusingspectrophotometricmethodisadifficultproblem,duetospectral interferences. By multivariate calibration methods such as partial least squares (PLS), it is possible to obtainamodeladjustedtotheconcentrationvaluesofthemixturesusedinthecalibrationrange.Orthogonal signal correction (OSC) is a preprocessing technique used for removing the information unrelated to the target variables based on constrained principal component analysis. OSC is a suitable preprocessing method for PLS calibration of mixtures without loss of prediction capacity using spectrophotometric method. In this study, the calibration model is based on absorption spectra in the 360–660nm range for 25 different mixtures of mercury and palladium. Calibration matrices were containing 0.025–1.60 and 0.05–0.50gmL−1 of mercury and palladium, respectively. The RMSEP for mercury and palladium with OSC and without OSC were 0.013, 0.006 and 0.048, 0.030, respectively. This procedure allows the simultaneousdeterminationofmercuryandpalladiuminsyntheticandrealmatrixsamplesgoodreliabilityof the determination.