The purpose of this study was to develop a quantitative structure–property relationship(QSPR) model based on the enhanced replacement method(ERM) and support vector machine(SVM) to predict the blood-to-brain barrier partitioning behavior(log BB) of various drugs and organic compounds. Different molecular descriptors were calculated using a dragon package to represent the molecular structures of the compounds studied. The enhanced replacement method(ERM) was used to select the variables and construct the SVM model. The correlation coefficient, R~2, between experimental results and predicted log BB was 0.878 and 0.986, respectively. The results obtained demonstrated that, for all compounds, the log BB values estimated by SVM agreed with the experimental data, demonstrating that SVM is an effective method for model development, and can be used as a powerful chemometric tool in QSPR studies. The purpose of this study was to develop a quantitative structure-property relationship (QSPR) model based on the enhanced replacement method (ERM) and support vector machine (SVM) to predict the blood-to-brain barrier partitioning behavior Various molecular and descriptors were calculated using a dragon package to represent the molecular structures of the compounds studied. The enhanced replacement method (ERM) was used to select the variables and construct the SVM model. The correlation coefficient, R ~ 2, between experimental results and predicted log BB was 0.878 and 0.986, respectively. The results give the, for all compounds, the log BB values ​​estimated by SVM agreed with the experimental data, demonstrating that SVM is an effective method for model development, and can be used as a powerful chemometric tool in QSPR studies