Abstract: The present invention relates to a method for preparing the crystal of human derived TRAIL protein and TRAIL receptor protein sDR5 complex and the crystal of TRAIL-sDR5 complex prepared by the method. The present invention also TRAIL relates to a three-dimensional structure of TRAIL protein in the form of complex with TRAIL receptor sDR5 as well as TRAIL protein itself, and specific residues existed in the contact central region of AA″ loop. The three-dimensional structure of TRAIL-sDR5 complex and the specific residues in the AA″ loop of the present invention can be effectively used for not only the development of TRAIL protein having the better cytotoxic activity and having the improved receptor biding affinity, which specifically kills viral infected cells or cancer cells but also molecular strategy for regulating the binding specificity between TNF and TNFR family.