HLA-G (human leukocyte antigen-G) is a non-classical HLA class I molecule, playing an important immuno-modulatory role in maintaining maternal immune tolerance of the semiallogenic fetus and organ transplantation. In this study, the cDNA sequence of extracellular domain of HLA-G1 was subcloned into the pET28a vector and a soluble 35 kD fusion protein (His-sHLA-G1) with six histine residues was obtained. In the 4 h 51Cr-release assay the fusion protein obviously inhibited the cytotoxicity of NK92 cells in a dose-dependent manner. These results indicated that sHLA-G1, as an activated immunoinhibitor, may provide an effective approach to overcoming the immune rejection of transplantation.