A quantitative structure-property relationship study was performed on the critical micelle concentration (cmc) of nonionic surfactants using the CODESSA program. A known correlation between the logarithm of the cmc and counts of linear alkane carbon atoms and ethoxy groups in linear alkyl ethoxylates was improved (R(2) = 0.996) by adding cross terms of these molecular descriptors. A general three-parameter structure-property relationship was developed for a diverse set of 77 nonionic surfactants (R(2) = 0.984) employing topological descriptors calculated for the hydrophobic fragment of the surfactant molecule. The three descriptors represent contributions from the size of the hydrophobic group, the size of the hydrophilic group, and the structural complexity of the hydrophobic group.