Development of reliable and efficient alternative in vivo methods for evaluation of the chemicals with potential neurotoxicity is an urgent need in the early stages of drug design. In this investigation, the computational prediction models for drug-induced neurotoxicity were developed by using the classical naïve Bayes classifier. Eight molecular properties closely relevant to neurotoxicity were selected. Then, 110 classification models were developed with using the eight important molecular descriptors and 10 types of fingerprints with 11 different maximum diameters. Among these 110 prediction models, the prediction model (NB-03) based on eight molecular descriptors combined with ECFP_10 fingerprints showed the best prediction performance, which gave 90.5% overall prediction accuracy for the training set and 82.1% concordance for the external test set. In addition, compared to naïve Bayes classifier, the recursive partitioning classifier displayed worse predictive performance for neurotoxicity. Therefore, the established NB-03 prediction model can be used as a reliable virtual screening tool to predict neurotoxicity in the early stages of drug design. Moreover, some structure alerts for characterizing neurotoxicity were identified in this research, which could give an important guidance for the chemists in structural modification and optimization to reduce the chemicals with potential neurotoxicity. Copyright © 2020 Elsevier Ltd. All rights reserved.