Receptor tyrosine kinase MET and its ligand hepatocyte growth factor (HGF) play crucial roles in many human malignancies. Numerous drugs have been developed against kinase center of MET or HGF-mediated activation; however， the outcomes in patients are not so promising. Increasing evidence show that MET has kinase-independent effects on tumorigenesis and dissemination， which explains the low efficacy in kinase inhibition-based strategy. VHH is the recombinant variable region of heavy-chain antibody. As a nanoscale antigen-binding unit， VHH has become an appealing drug candidate in cancer therapy. In our study， we choose a novel strategy to construct an anti-MET VHH pool against the whole ecto-domain of MET. Comparing to monoclonal antibody or single VHH， the anti-MET VHH pool strongly promotes MET degradation through Clathrin-dependent endo-lysosomal pathway. Thus， the anti-MET VHH pool not only blocks kinase activity of MET， but also reduces protein level of MET. As a consequence， anti-MET VHH pool dramatically suppresses cancer cell proliferation， viability， and colony formation ， and inhibits tumorigenesis and growth in mice. Taken together， VHH pool-based strategy greatly improves MET-targeted therapeutic effects on cancer.