By carrying out density functional theory calculations, we have performed a detailed mechanism study for the cycloisomerization reaction of 4-phenyl-hexa-1,5-enyne catalyzed by homogeneous gold to better understand the observed different catalytic activity of several catalysts, including (PPh3)AuBF4, (PPh3)AuCl, AuCl3, and AuCl. In all situations, the reaction is found to involve two major steps: the initial nucleophilic addition of the alkynyl onto the alkene group and the subsequent 1,2-H migration. It is found that the potential energy surface profiles of systems are very different when different catalysts are used. For (PMe3)AuBF4- and (PMe3)AuCl-mediated systems, the nucleophilic addition is the rate-determining step, and the calculated free energy barriers are 15.2 and 41.9 kcal/mol, respectively. In contrast, for AuCl3- and Au Cl-mediated systems, the reactions are controlled by the dissociations of catalysts from the product-like intermediates, and the calculated dissociation energies are 18.1 and 21.7 kcal/mol, respectively, which are larger than both the corresponding free energy barriers of the nucleophilic addition and the H-migration processes (8.5 and 7.3 kcal/mol for the AuCl3-mediated reaction, and 16.9 and 11.3 kcal/mol for the Au Cl-mediated reaction). These results can rationalize the early experimental observations that the reactant conversion rates are 100, 0, and 50% when using (PPh3)AuBF4, (PPh3)AuCl, and AuCl3 as catalysts, respectively. The present study indicates that both the ligand and counterion of homogeneous Au catalysts importantly influence their catalytic activities, whereas the oxidation state of Au is not a crucial factor controlling the reactivity.