The group of nine antipsychotic drugs (chlorpromazine, chlorprothixene, clozapine, quetiapine, perazine, perphenazine, prochlorperazine, promazine, trifluoperazine) was analyzed with the use of thin-layer chromatography. As stationary phases silica gel and amino-modified plates were applied. Secondarily, aqueous and nonaqueous binary mobile phases composed of: tetrahydrofuran and petroleum ether, methanol and petroleum ether, tetrahydrofuran and water were used. In order to calculate molecular descriptors HyperChem, ChemAxon and ACD/labs software were used. Based on obtained chromatographic data, the quantitative structure- retention relationship (QSRR) equations were established with the use of multiple linear regression. In addition, cluster analysis was applied. The attained QSRR equations have satisfactory statistical parameters and present molecular mechanism of examined chromatographic systems. Furthermore, this analysis suggests that charge max and HOMO energy could significant influence lipophilic properties of antipsychotic drugs.