We newly developed a hybrid protein, tentatively named human MIKO-1 (hM1), based on the amino acid sequences of human S100A8 (hS100A8) and hS100A9. Human macrophage-like cells (hMΦ), which were differentiated from THP-1 cells by phorbol 12-myristate 13-acetate, were used to investigate the immune function of hM1 and its dynamic mobility in cells. Western blotting was conducted to detect hM1 in the cytoplasm and nucleus of hMΦ. A polymerase chain reaction (PCR) and quantitative PCR were performed to examine changes in the mRNA levels of proinflammatory cytokines in hMΦ. Fluorescent immunochemical staining was conducted to microscopically observe the intracellular behavior of hM1 in hMΦ, together with hS100A8 and/or hS100A9. Microscopic observations showed that hM1 rapidly bound to activated hMΦ and immediately migrated even inside the nucleus of these cells. The intracellular localization of hM1 in hMΦ almost coincided with that of hS100A8, suggesting the close involvement of hS100A8 in the intracellular behavior of hM1 in hMΦ. The mRNA expression of each proinflammatory cytokine was significantly suppressed in hMΦ preliminarily treated with hM1 despite a subsequent stimulation with lipopolysaccharide. Significant decreases in the mRNA levels of proinflammatory cytokines in hMΦ strongly suggest the potential of hM1 as a negative regulator of inflammation. hM1 may land on a special site on the DNA chain, such as the NF-κB motif, in the nucleus to directly inhibit the mRNA expression of proinflammatory cytokines. In conclusion, hM1 is a prominent player that significantly attenuates the cytokine storm caused by excessively activated hMΦ.