The oxidation of ethylbenzene (EB) using tert-butyl hydroperoxide as the oxidizing agent was carried out in presence of gold nanoparticles (3 nm) supported on zinc oxide in acetonitrile solution. A higher selectivity towards acetophenone (ACP) as the major product, and a moderate selectivity towards other products such as 1-phenylethanol (PE), benzaldehyde (BZL), and benzoic acid (BzA) were observed using the prepared Au/ZnO nanocatalysts at 100 °C for 24 h. It is suggested the reaction produces an intermediate product, which is dimethylethyl-1-phenylethyl peroxide through a radical mechanism. A small amount of benzaldehyde was observed because benzaldehyde went autoxidation to form benzoic acid with the presence of oxidation agent of TBHP during reaction. The factors affecting the catalytic activity such as gold loading, calcination treatment at 300°C, type of solvent, reaction time, reaction temperature, oxidant to substrate molar ratio, catalyst weight, and solvent volume were studied. The gold nanoparticle catalyst synthesized by deposition precipitation method using urea was characterized by XRD, HRTEM, ATR-IR, XRF, and BET and offers a very selective reaction pathway for the oxidation of ethylbenzene.