The chemical analysis of spent nuclear fuel (SNF) reprocessing is a very challenging research field due to the high radioactivity of process streams and their complex composition. The process managing requires thorough chemical analysis to ensure safe and efficient performance. Traditional ways of chemical control of SNF reprocessing are based on sampling methods and involve long and tedious procedures, failing to provide immediate information on the process status. Recent literature suggests that potentiometric multisensor systems can be employed for on-line control. However, up to now these systems were only studied in very simple model media. This work reports on the potentiometric multisensor array applied for the first time for the simultaneous quantification of the content of actinides (uranium, plutonium, neptunium) and several other analytes (zirconium, molybdenum and nitric acid) in the complex samples obtained from the pilot extraction unit for SNF reprocessing. The same samples were also analyzed by UV-Vis spectrometry (another prospective method for on-line control) and the analytical performance of these two methods was compared using established analytical figures of merit (sensitivity and analytical sensitivity metrics) for multivariate calibration. In spite of the extremely challenging analytical task, both simple methods provide the characteristics suitable for real industrial applications. © 2023 Elsevier B.V.