Benzene hydroxylation catalyzed by ruthenium-substituted Keggin-type polyoxometalates [RuV(O)XW11O39] (RuOX; X = Al, Ga, Si, Ge, P, As, S; heteroatoms; 3 ≤ n ≤ 6) is investigated using the density functional theory approach. As a possible side reaction, the water oxidation reaction is also considered. We found that the rate-determining step for water oxidation by RuOX requires a higher activation free energy than the benzene hydroxylation reaction, suggesting that all of the RuOX catalysts show high chemoselectivity toward benzene hydroxylation. Additionally, the heteroatom effect in benzene hydroxylation by RuOX is discussed. The replacement of Si by X induces changes in the bond length of μ4O-X, resulting in a change in the activation free energy for benzene hydroxylation by RuOX. Consequentially, RuOS is expected to be the most effective catalyst among the (RuOX) catalysts for the benzene hydroxylation reaction.