The activation of ethanol and methanol by VO2(+) in gas phase has been theoretically investigated by using density functional theory (DFT). For the VO2(+)/ethanol system, the activation energy (ΔE) is found to follow the order of ΔE(C(β)-H) < ΔE(C(α)-H) ≈ ΔE(O-H). Loss of methyl and glycol occurs respectively via O-H and C(β)-H activation, while acetaldehyde elimination proceeds through two comparable O-H and C(α)-H activations yielding both VO(H2O)(+) and V(OH)2(+). Loss of water not only gives rise to VO(CH3CHO)(+) via both O-H and C(α)-H activation but also forms VO2(C2H4)(+) via C(β)-H activation. The major product of ethylene is formed via both O-H and C(β)-H activation for yielding VO(OH)2(+) and VO2(H2O)(+). In the methanol reaction, both initial O-H and C(α)-H activation accounts for formaldehyde and water elimination, but the former pathway is preferred.