Homeobox (Hox)-containing genes have been identified as regulators which control the expression of a variety of genes involved in development and differentiation. Recent reports also suggested an involvement of Hox genes in transformation and/or tumor progression. In human prostate cancer, overexpression of HOXC8 was associated with a loss of tumor differentiation, which implies the involvement of HOXC8 in the process leading to the tumorigenicity of tumor cells. In order to investigate the role of Hoxc8 in the growth of tumor cells, Hoxc8 was designed to be expressed constitutively in B16F10 melanoma cells after stable transfection, and then a clone B16F10Shoxc8#14 overexpressing Hoxc8 was selected and analyzed further. B16F10Shoxc8#14 expressed Hoxc8 at high level and exhibited a reduced growth rate in vitro. When the cell cycle progress was analyzed, it has a decreased S phase population through upregulation of cell cycle regulators, such as p21, HDAC8 and E2F5. When the effect of Hoxc8 was analyzed on tumor growth in vivo C57BL/6 mice, the tumorigenicity as well as the growth rate was significantly decreased, indicating that the overexpression of Hoxc8 in B16F10 melanoma inhibits the tumor proliferation, probably functioning as a cell cycle regulator.