Derived from 149 hydrophobic factors of 20 natural amino acids, a novel amino acid descriptor termed as generalized hydrophobicity scale (GH-scale) was proposed by principal component analysis (PCA). Via genetic algorithm-partial least square (GPLS) method, quantitative structure-activity relationship (QSAR) model was constructed by GH-scale for 152 human leukocyte antigen (HLA)-A*0201-restricted cytotoxic T lymphocyte (CTL) epitopes with the model estimated and cross-validated correlative coefficients of R2 = 0.813 and Q2 = 0.725, respectively. It was in- dicated that hydrophobic interaction played an im- portant role in HLA-A*0201-CTL interaction, promi- nently at anchor residues. Derived from 149 hydrophobic elements of 20 natural amino acids, a novel amino acid descriptor termed as generalized hydrophobicity scale (GH-scale) was proposed by principal component analysis (PCA). Via genetic algorithm-partial least square (GPLS) method, quantitative structure -activity relationship (QSAR) model was constructed by GH-scale for 152 human leukocyte antigen (HLA) -A * 0201-restricted cytotoxic T lymphocyte (CTL) epitopes with the model estimated and cross-validated correlative coefficients of R2 = 0.813 and Q2 = 0.725, respectively. It was in- dicated that the hydrophobic interaction played an im- portant role in HLA-A * 0201-CTL interaction, promi- nently at anchor residues.