The hydrophobic adsorption of three series of small peptides on commercial Octyl-Sepharose resins were investigated. The adsorption of tryptophan containing peptides was found to be driven by enthalpy. The enthalpy of adsorption on Octyl-Sepharose per tryptophan residue was approximately -9.4 similar to -11.8 kJ/mol. Meanwhile, it was found that the hydrophobic adsorption of aliphatic amino acids was probably driven by entropy. When we inserted an aliphatic amino acid into a tryptophan containing peptide, both the adsorption enthalpy and entropy increased compared to the adsorption of a peptide inserted along with glycine at the same position. The results suggested that the hydrophobic adsorption of aliphatic amino acids was entropy driven. Apparently, the direct interactions between octyl chains and aliphatic amino acids were weak, but those between octyl chains and tryptophans are particularly strong.