Angiogenin is an angiogenic factor involved in tumorigenesis.However, the mechanism of angiogenin’s action remains elusive. In the present study, we identified fibulin 1, an extra-cellular matrix and plasma glycoprotein, as an angiogenin-interacting molecule by yeast two-hybrid screening. This interaction was further confirmed by two different approaches. First, fibnlin 1 was co-immunoprecipitated with angiogenin by anti-angiogenin monoclonal antibody in vitro,suggesting angiogenin binds with fibulin 1 directly. Then fluorescence resonance energy transfer analysis showed that fibulin 1 interacted with angiogenin in COS-7 cells, showing that the binding could occur in a cellular context. As fibulin 1 plays an important role in cell proliferation, migration,adhesion, and stabilizes new-forming blood vessel wall, the interaction between fibulin I and angiogenin might under-line one possible mechanism of angiogenin in angiogenesis and/or tumorigenesis.