In closed hydroponics, fast and continuous measurement of individual nutrient concentrations is necessary to improve water-and nutrient-use efficiencies and crop production. Ion-selective electrodes (ISEs) could be one of the most attractive tools for hydroponic applications. However, signal drifts over time and interferences from other ions present in hydroponic solutions make it difficult to use the ISEs in hydroponic solutions. In this study, hybrid signal processing combining a two-point normalization (TPN) method for the effective compensation of the drifts and a back propagation artificial neural network (ANN) algorithm for the interpretation of the interferences was developed. In addition, the ANN-based approach for the prediction of Mg concentration which had no feasible ISE was conducted by interpreting the signals from a sensor array consisting of electrical conductivity (EC) and ion-selective electrodes (NO 3 , K, and Ca). From the application test using 8 samples from real greenhouses, the hybrid method based on a combination of the TPN and ANN methods showed relatively low root mean square errors of 47.2, 13.2, and 18.9 mg·L −1 with coefficients of variation (CVs) below 10% for NO 3 , K, and Ca, respectively, compared to those obtained by separate use of the two methods. Furthermore, the Mg prediction results with a root mean square error (RMSE) of 14.6 mg·L −1 over the range of 10-60 mg·L −1 showed potential as an approximate diagnostic tool to measure Mg in hydroponic solutions. These results demonstrate that the hybrid method can improve the accuracy and feasibility of ISEs in hydroponic applications.