The synthesis of phenol by one-pot oxidation of benzene with dioxygen (O2) is a significant conceptual and practical challenge because benzene has low reactivity to O2 at room temperature and ambient pressure. Furthermore, phenol is more reactive than benzene and is easily overoxidized, so complete oxidation is more likely to proceed in the benzene oxidation reaction, which generally results in lower phenol yield and selectivity. Herein, we report that a heteropolyacid H3PW12O40 functions as a photocatalyst for benzene oxidation reaction in an aqueous acetonitrile solution using O2 in high phenol yield (23–41%) and selectivity (80–90%). The addition of acetonitrile to the reaction solution significantly inhibited the complexation between phenol and H3PW12O40, preventing phenol overoxidation. Furthermore, no decomposition of H3PW12O40 during the reaction was evidenced by UV–VIS spectra. This photocatalyst can be used repeatedly with only a slight decrease in the rate of phenol formation. For the mechanistic study, the initial rates, which depended on the reaction conditions, were investigated in detail. The benzene oxidation under anaerobic conditions was also conducted as a control experiment. A color change of reaction solution from colorless to blue has confirmed the reduction of H3PW12O40 during the catalytic process and the formation of reduced H3PW12O40 detected in the UV–VIS spectra. A kinetic isotope effect (KIE), kH/kD = 1.15, is found for the oxidation of benzene/benzene‑d6, indicating electron transfer is the principal C−H bond activation process in the mechanism. We identified hydrogen peroxide as an intermediate and found that phenol was generated in both the photocatalytic reduction and reoxidation process in our system.