Aerobic granulation can be regarded as a microorganism-to-microorganism self-immobilization process, in which cell hydrophobicity could be a decisive parameter in determining the microorganism-to-microorganism interaction and structural compactness of aerobic granules. This study looked into the thermodynamic interpretation of cell hydrophobicity in aerobic granulation; and a model that correlates microbial interaction and relative cell hydrophobicity defined as the ratio of cell hydrophobicity over cell hydrophilicity was derived. This model describes how cell hydrophobic and hydrophilic interactions affect aerobic granulation and offers deep insights into the thermodynamic mechanisms of microbial aggregation. The model prediction was in good agreement with experimental data. Results showed that aerobic granulation was a function of cell hydrophobicity over cell hydrophilicity, i.e. a high cell hydrophobicity strongly favors microbial aggregation and results in a more compact structure.