Chiral hydantoins display potential antidepressant and anticancer activities. The quantitative structure property relationship (QSPR) study on chiral compounds plays a key role in predicting the retention factor and the separation factor even the elution order of the enantiomers. In this study, the structures of chiral arylhydantoin compounds have been built to compute molecular structural parameters using VolSurf program. The satisfying models were established between the parameters and the retention factor as well as the separation factor. Analysis on the variables shows that the large difference values of volume, hydrophilic regions and hydrogen bond acceptor and donor regions at some energy levels will result in the large separation factor. The differences of hydrophobic regions and the unbalance between the centre of mass and the barycentre of the hydrophobic region at high energy levels are also favorable to the separation. The differences of surface area, hydrophilic regions and hydrogen bond acceptor and donor regions at other energy levels as well as hydrophobic regions and the unbalance at low energy levels between the enantiomers are disadvantageous to the separation. The analysis on the chiral recognition mechanism demonstrates that the differences of the interaction energies between the enantiomers are mainly affected by the hydrogen bond, π-π interaction and CH3-π interaction. The retention factor and the separation factor, especially the elution order of the enantiomers can be easily predicted using the models. The study provides a helpful guidance for studying other chiral compounds.