Abstract: Pd-catalyzed oxidative C-H/C-H coupling reaction is an emerging type of C-H acti-vation reaction, which attracts great interests because both reaction partners do not re-quire pre-functionalization. In the present study, we employed DFT methods to investigatethe mechanism of Pd(OAc)₂-catalyzed oxidative C-H/C-H coupling of pentafluoroben-zene with benzene. Four possible pathways were examined in the C-H activation part: path A benzene-pentafluorobenzene mechanism (C-H activation of benzene occurs before the C-H activation of pentafluorobenzene), path B pentafluorobenzene-benzene mechanism (C-H activation of benzene occurs after the C-H activation of pentafluorobenzene), path C benzene-pentafluorophenylsilver mechanism (C-H activation of benzene and subsequenttransmetalation with pentafluorophenyl silver complex), path D pentafluorophenylsilver-benzene mechanism (transmetalation with pentafluorophenyl silver complex and subsequent C-H activation of benzene). Based on the calculations, the sequences of two C-H activation steps are found to be different in the oxidative couplings of same substrates (i.e. pentaflu-orobenzene and benzene) in different catalytic systems, where the additive Ag salts played a determinant role. In the absence of Ag salts, the energetically favored pathway is path B (i.e. the C-H activation of pentafluorobenzene takes place before the C-H cleavage of benzene). In contrast, with the aid of Ag salts, the coordination of pentafluorophenylsilver to Pd center could occur easily with a subsequent C-H activation of benzene in the second step, and the second step significantly raises the whole reaction barrier. Alternatively, in thepresence of Ag salts, the kinetically preferred mechanism is path C (i.e. the C-H activation of benzene takes place in the first step followed by transmetalation with pentafluorophenyl-silver complex), which is similar to path A. The calculations are consistent with the H/D exchange experiment and kinetic isotope effects. Thus the present study not only offers a deeper understanding of oxidative C-H/C-H coupling reaction, but also provides helpful insights to further development of more efficient and selective oxidative C-H/C-H coupling reactions.