Eleven known caged polyprenylated xanthones 1-11 were isolated from the resin of Garcinia hanburyi Hook. f., and their structures were identified by their MS, NMR and UV spectra. These xanthones showed significant cytotoxicities against four human cancer cell lines (HeLa, A549, HCT-116, and HepG-2) and strong inhibition against the proliferation of the HUVEC cell line in vitro by the MTT method. Furthermore, in an in vivo zebrafish model, xanthones 3 (morellic acid), 7 (gambogenin) and 9 (isogambogenic acid) showed comparable antiangiogenic activities with less toxicities than xanthone 1 (gambogic acid), as evaluated by death and heart rates of treated zebrafish. Xanthone 7 exhibited antiangiogenic activity with no toxicity at concentrations ranging from 8 µM to 16 µM. Meanwhile, xanthones 1, 3, 7 and 9 strongly inhibited the migration of HUVEC at a low concentration of 0.5 µM in HUVEC cell migration assay in vitro. Taken together, these findings strongly suggest that xanthone 7 might be a novel angiogenesis inhibitor.