Based on DFT calculations, the catalytic mechanism of palladium(0) atom, commonly considered as the catalytic center for Sonogashira cross-coupling reactions, has been analyzed in this study. In the cross-coupling reaction of iodobenzene with phenylacetylene without co-catalysts and bases involved, mechanistically plausible catalytic cycles have been com- putationally identified. These catalytic cycles typically occur in three stages: 1) oxidative addition of an iodobenzene to the Pd(0) atom, 2) reaction of the product of oxidative addition with phenylacetylene to generate an intermediate with the Csp bound to palladium, and 3) reductive elimination to couple the phenyl group with the phenylethynyl group and to regenerate the Pd(0) atom. The calculations show that the first stage gives rise to a two-coordinate palladium (II) intermediate (ArPdI). Starting from this intermediate, the second oxidative stage, in which the C–H bond of acetylene adds to Pd(II) without co-catalyst involved, is called alkynylation instead of transmetalation and proceeds in two steps. Stage 3 of reductive elimination of diphenylacetylene is energetically favorable. The results demonstrate that stage 2 requires the highest activation energy in the whole catalysis cycle and is the most difficult to happen, where co-catalysts help to carry out Sonogashira coupling reaction smoothly.