The present invention discloses a monoclonal antibody against the extracellular domain of human tumor necrosis factor-related apoptosis-inducing ligand receptor DR5 (death receptor 5), The present invention also provides a method of producing the monoclonal antibody, amino acid sequences of the variable regions of the monoclonal antibody's heavy chain and light chain, as well as use of the monoclonal antibody for preparation of a medicament in the treatment of various cancers and /or AIDS.