We have reported that the levels of the soluble molecule of the human leukocyte antigen class I (sHLA-I) in patients with advanced gastric cancer were significantly lower than those in patients with cancer in the early stages. However, the effect of sHLA-I on gastric cancer cells has not been elucidated. Using human gastric cancer cell lines, MKN28, MKN45, and MKN74, we evaluated the effects of sHLA-I on cell growth, DNA synthesis, and apoptosis induction. Three types of synthesized peptides derived from HLA-I were also examined for their capacity to induce apoptosis. sHLA-I and a synthesized peptide, nos. 220-232 of the alpha3 domain of HLA-B7, caused cell growth inhibition by inducing apoptosis in human gastric cancer cells. This peptide also inhibited the in vivo growth of cancer dissemination caused by an intraperitoneal injection of MKN45 into severe combined immunodeficient mice. In conclusion, sHLA-I and the peptides derived from HLA-I cause apoptosis in human gastric cancer cell lines.