The σ···π interactions in the Au6···PhX (X=H, CH3, OH, OCH3, NH2, F, Cl, Br, CN, NO2) complexes are studied using quantum chemical methods. The present study focuses on the different effects of electron-donating and -withdrawing substituent. The structure and binding strength of the complexes are examined. The interactions between Au6 cluster and various substituted benzene become strengthened relative to the Au6···benzene complex. The interaction region indicator analysis was performed, and the interaction region and interaction between the substituent and Au6 cluster are discussed. It is found that the substituent effects on the σ···π interactions between Au6 cluster and substituted benzene are different from π···π interactions of benzene dimer. Energy decomposition analysis was carried out to study the nature of σ···π interactions, and the substituent effects are mainly reflected on the electrostatic interaction and dispersion.