The present invention provides a humanized monoclonal antibody against extracellular domain of human death receptor 5, comprising a light chain variable region, whose amino acid sequence has at least 90% identity with the amino acid sequence shown as SEQ ID NO: 1, a heavy chain variable region, whose amino acid sequence has at least 90% identity with the amino acid sequence shown as SEQ ID NO: 2, and constant region derived from human antibody. The present invention also provides nucleotide sequence encoding said humanized monoclonal antibody, a recombinant eukaryotic expression vector, a process for preparing the humanized monoclonal antibody, and the composition and use therefore. Said humanized monoclonal antibody of the present invention shows specific apoptosis-inducing activity against various cancer cells both in vivo and in vitro, and thus it can be used alone or in combination with natural ligand of DR5, apoptosis-inducing ligand associated with tumor nerosis factor or other medicaments for the treatment of a variety of cancers as well as other diseases associated with high DR5 expression.