In an attempt to improve the stability of tumor necrosis factor-related apoptosis inducing ligand ( TRAIL), we prepared the nano-sized complexes by mixing the positively charged TRAIL with heparin, a highly sulfated polysaccharide. The increase in the feed ratio (FR) of heparin to TRAIL reduced the particle size and decreased the zeta-potential, indicating that the TRAIL surface was covered by heparin via the ionic interactions. TRAIL in the complexes was demonstrated to effectively induce apoptosis of the cancer cells. The results indicated that heparin is the useful, anionic polysaccharide as the carrier of TRAIL to form stable nano-sized complexes.