A one-pot synthetic approach for the preparation of poly(2,6-dimethyl-1,4-phenylene oxide)/polystyrene (PPO/PS) alloy in aqueous medium was developed. The method was based on the combination of the oxidative coupling polymerization of 2,6-dimethylphenol (DMP) to form PPO in the presence of a reactive swelling agent, styrene (St), and in situ reverse atom transfer radical polymerization (RATRP) of St initiated by 2,2′-azobis[2-(2-imidazolin-2-yl)propane] dihydrochloride (AIBI) in alkaline aqueous solution. The complex of CuCl2 and 4-dimethylaminopyridine (DMAP) was utilized as the catalyst to catalyze the two types of polymerization mentioned above. Oxygen was employed as the sole oxidant to synthesize PPO. The introduction of St during the oxidative polymerization of DMP could increase the molecular weight of PPO. Finally thermodynamically compatible PPO/PS alloy was successfully prepared.