With the advancement of minimally invasive interventional therapy, biological heart valves (BHVs) have been extensively used in clinics. However, BHVs are generally prone to degeneration within 10-15 years after implantation due to defects including cytotoxicity, immune response, calcification and thrombosis, which are closely related to glutaraldehyde-crosslinking. In this work, we prepared a functionalized BHV through the in situ polymerization of methacrylated porcine pericardium and 2-hydroxyethyl methacrylate to avoid and overcome the defects of glutaraldehyde-crosslinked BHVs. The functionalized BHV was proven to be stable against enzymatic degradation and compatible towards HUVECs. After implantation in rats subcutaneously, a significantly mitigated immune response and reduced calcification were observed in the functionalized BHV. With the grafting of hydrophilic 2-hydroxyethyl methacrylate polymers, the antithrombogenicity of BHV was markedly enhanced by resisting the unfavorable adhesion of blood components. Moreover, the hydrodynamics of the functionalized BHV totally conformed to ISO 5840-3 under a wide range of simulated physiological conditions. These results indicate that the functionalized BHV with enhanced biocompatibility, anticalcification property and antithrombogenicity exhibited a low risk of degeneration and should be explored for further application.