A multiparameter quantitative model was developed to establish a relationship between structural descriptors of a set of 52 ionic liquids and their E T N polarity scale. Theoretical descriptors were extracted by Dragon software and the E T N model was obtained using multiple linear regression approach. After molecular modeling, four significant descriptors were identified which are related to the E T N values of the ionic liquids and demonstrates good fit statistics and accurate predictions. The stability and prediction ability of the E T N model was evaluated using various common statistical methods such as cross-validation, external validation, and Y-randomization test. As another indicator of model’s validity, the leverage and standardized residual confirmed the presence of almost all 52 ILs in the applicability domain of the proposed model.