In this study, photocatalytic degradation of 2-nitrophenol and 4-nitrophenol were carried out efficiently using ZnO nanoparticles photo-catalyst under simulated solar irradiation. The photo-decomposition processes were optimized simultaneously by employing central composite design and multivariate curve resolution alternating least squares. The effective factors were as follows: the amount of the nano-photo-catalyst, the concentration of 2-NP and 4-NP, the volume of H₂O₂ and temperature. Since both analytes have acid–base properties, the pH-dependency of the kinetic processes were investigated by conducting each experiment under both acidic and basic conditions, where only the protonated or deprotonated forms of the analytes were present in the solution. Each experiment was monitored spectrophotometrically and then suitable chemometrics approaches were applied to the data to discover underlying photo-decomposition reactions. A new and simple criterion based on the standard deviation of a kinetic profile was proposed as a degradation index for quantifying the progress of nitrophenols decomposition processes and considered as a response in the experimental design analysis. The results revealed that acidic and basic forms of both nitrophenols were involved in three-step consecutive reactions during degradations, but the kinetic rate constants of the processes were really different, a fact, which resulted in different optimal conditions for acid and basic media.