A novel inhibitor of angiogenesis named SCAIF80 (shark cartilage-derived angiogenesis inhibitory factor) from shark cartilage has been isolated and characterized. SDS-PAGE analysis followed by silver staining revealed a single band with molecular weight (M(r)) of 80 kD. To determine whether this protein was capable of inhibiting angiogensis, it was assayed in endothelial cell (EC) proliferation and migration assay. The results showed that SCAIF80 significantly suppressed EC proliferation and migration in a dose-dependent manner. In the chick chorioallantoic membrane (CAM) assay, SCAIF80 also showed a potent inhibitory activity on angiogenesis in vivo. In animal tests, the growth of tumor was potently suppressed by SCAIF80 therapy. Lewis lung carcinoma was inhibited by 93.83 % at a dose of 5 mg/(kg.d). These findings suggest that shark cartilage may produce a novel protein with anti-angiogenic and anti-tumor activity.