A simple, novel and sensitive spectrophotometric method was described for simultaneous determination of nitrophenol isomers mixtures. All factors affecting on the sensitivity were optimized and the linear dynamic range for determination of nitrophenol isomers were found. The simultaneous determination of nitrophenol mixtures by using spectrophotometric methods is a difficult problem, due to the spectral interferences. The partial least squares modeling was used for the multivariate calibration of the spectrophotometric data. The orthogonal signal correction was used for preprocessing of data matrices and the prediction results of model, with and without using orthogonal signal correction, were statistically compared. The experimental calibration matrix was designed by measuring the absorbance over the range 300-520 ran for 21 samples of 1-20, 1-20 and 1-10 mu g ml(-1) of m-nitrophenol, o-nitrophenol and p-nitrophenol, respectively. The RMSEP for m-nitrophenol, o-nitrophenol and p-nitrophenol with and without OSC were 0.3682, 0.5965, 0.3408 and 0.7351, 0.9962, 1.0055, respectively. The proposed method was successfully applied for the determination of m-nitrophenol, o-nitrophenol and p-nitrophenol in synthetic and real matrix samples such as water. (C) 2007 Elsevier B.V. All rights reserved.