In this study, noncovalent interactions between aromatic groups and side-chain amides in proteins were characterized. To elucidate the nature and structure-strength relationship of the interaction, the geometries and interaction potential energy surfaces for the benzene-formamide model complex were exhaustively and systematically studied at the MP2 level of theory. The effects of basis set size and basis set superposition error were investigated for 15 selected complex structures. The results indicate that the aromatic-amide (side-chain) interaction can achieve a significant binding energy of up to 4.0 kcal/mol over a wide conformational space. The interaction involves the entire side-chain amide group rather than only its amine portion. Both dispersion and electrostatic interactions are the major contributors for the binding energy, and the pi electron charge distributions in both groups and the dipole moment of the side-chain amide group are crucial to the interaction. The importance of such an interaction in proteins was verified through data mining analyses of 1029 X-ray protein structures. The interaction naturally occurs in proteins with a frequency of more than one per two proteins on a statistical average and is of significance for some protein structure. The interaction was also found to play a role in determining the biological activity of some proteins. Our study not only emphasizes the significance of aromatic-amide(side-chain) interactions in proteins but also deepens our understanding of noncovalent interactions involving benzene or other aromatic groups.