Hypoxia-inducible　factor-1　(HIF-1)　is　a　transcription　factor　that　is　activated　upon　exposure　to　hypoxic　stress.　It　modulates　a　number　of　cellular　responses　including　proliferation,　apoptosis,　angiogenesis,　and　metabolism　by　activating　a　panel　of　target　genes　in　response　to　hypoxia.　The　HIF-1　level　is　often　upregulated　in　the　hypoxic　microenvironment　of　solid　tumors,　which　contributes　to　cancer　treatment　failure.　Here　we　report　that　silver　nanoparticles　(AgNPs),　which　are　widely　used　as　an　antimicrobial　agent,　are　an　effective　inhibitor　of　HIF-1.　AgNPs　inhibited　the　activation　of　a　HIF-dependent　reporter　construct　after　the　cells　were　exposed　to　hypoxic　conditions　or　treated　with　cobalt　chloride,　a　hypoxia　mimetic　agent.　The　AgNPs　also　interfered　with　the　accumulation　of　HIF-1　alpha　protein　and　the　induction　of　the　endogenous　HIF　target　genes,　VEGF-A　and　GLUT1.　Since　both　HIF-1　and　vascular　endothelial　growth　factor-A　play　an　important　role　in　angiogenesis,　AgNPs　also　inhibited　angiogenesis　in　vitro.　Our　data　reveal　a　new　mechanism　of　how　AgNPs　act　on　cellular　function,　that　is,　they　disrupt　HIF　signaling　pathway.　This　finding　provides　a　novel　insight　into　how　AgNPs　can　inhibit　cancer　cell　growth　and　angiogenesis.