An isolated anti-SCUBE2 antibody or a binding fragment thereof is disclosed. The anti-SCUBE2 antibody comprises an antigen binding region that specifically binds to a target domain located within SCUBE2 (SEQ ID NO: 66) and exhibits a property of inhibiting VEGF-induced angiogenesis. The target domain is selected from the group consisting of the EGF-like motifs 4 to 6 ranging from a.a. position 175 to 323, or the spacer region ranging from a.a. position 441 to 659, or the first cys-rich motif ranging from a.a. position 668 to 725 of SCUBE2 (SEQ ID NO: 66). The anti-SCUBE2 antibody or binding fragment thereof is for use in treating a disease associated with VEGF-induced angiogenesis, or for use in treating a tumor or inhibiting tumor angiogenesis and cancer cell growth in a subject in need thereof.