In this work, β-cyclodextrin was developed to prevent protein aggregation in foam fractionation using bovine serum albumin (BSA) as a model protein. The role of β-cyclodextrin in preventing the aggregation of BSA induced by the gas-liquid interface was studied at the molecular level. The results indicate that by holding the exposed phenylalanine residues in its hydrophobic cavity, β-cyclodextrin effectively prevented the aggregation of BSA induced by the gas-liquid interface in foam fractionation. Furthermore, β-cyclodextrin could be effectively separated from BSA in the foamate due to their weak association.