Heart valve replacement is an effective therapy for patients with moderate to severe valvular stenosis or regurgitation. Most bioprosthetic heart valves applied clinically are based on cross-linking with glutaraldehyde (GLUT), but they have some drawbacks like high cytotoxicity, severe calcification, and poor hemocompatibility. In this study, we focused on enhancing the properties of bioprosthetic heart valves by cross-linking with 3,4-dihydroxybenzaldehyde (DHBA). The experiment results revealed that compared with GLUT cross-linked porcine pericardium (PP), the relative amount of platelets absorbed on the surface of DHBA cross-linked PP decreased from 0.294 +/- 0.034 to 0.176 +/- 0.028, and the activated partial thromboplastin time (APTT) increased from 9.9 +/- 0.1 to 15.2 +/- 0.1 s, indicating improved hemocompatibility. Moreover, anticalcification performance and cytocompatibility were greatly enhanced by DHBA cross-linking. In conclusion, the properties of bioprosthetic valves could be effectively improved by processing valves with a DHBA-based cross-linking method.