In this study, the catalytic activity and stability of flowerlike hybrid horseradish peroxidase (HRP) nanobiocatalyst (HRP-Cu2+) obtained from Cu2+ ions and HRP enzyme in the polymerization reaction of guaiacol were analyzed. We demonstrated that HRP-Cu2+ and hydrogen peroxide (H2O2) initiator showed significantly increased catalytic activity and stability on the polymerization of guaiacol compared to that of free HRP enzyme. Poly(guaiacol) was observed with quite high yields (88%) and molecular weights (38,000 g/mol) under p11 7.4 phosphate-buffered saline (PBS) conditions at 60 degrees C. with 5 weight% of HRP-Cu2+ loading. HRP-Cu2+ also shows very high thermal stability and works even at 70 degrees C reaction temperature; free HRP enzyme denatures at that temperature. Furthermore, HRP-Cu2+ provided considerable repeated use and showed some degree of catalytic activity, even after the fourth recycle, in the polymerization of guaiacol.