Soluble polyphenol was synthesized for the first time by enzymatic oxidative polymerization of phenol using peroxidase and hydrogen peroxide as catalyst and oxidizing agent, respectively. A mixed sol vent of alcohol and buffer improved the polymer solubility toward N,N-dimethylformamide (DMF). The resulting polymer was composed of a mixture of phenylene and oxyphenylene units. Changing the solvent composition could control the molecular weight and regioselectivity of the polymer. The polymer was found to possess relatively high thermal stability.