Abstract H-rev107 is downregulated in many carcinomas and tumor cell lines. Using postconfluent NIH3T3 cells, we demonstrated that growth arrest caused by contact inhibition, but not serum deprivation, increased H-rev107 expression. Furthermore, histone deacetylase inhibitors induced H-rev107 expression in NIH3T3 cells and allowed its reexpression in H-rev107-deficient WEHI 7.1 lymphoma cells. In contrast, no effect of the postconfluent stage or histone deacetylase inhibitors on H-rev107 levels was observed in tumorigenic H-rev107-expressing cell lines, HepG2, HeLa, and SKBR3. Transfections showed that TSA treatment increased luciferase activity 20-fold in NIH3T3 cells. We found that the GC-box at −83/−75 is a key element for H-rev107 induction by TSA and growth arrest, although there were no changes in the pattern and intensity of Sp1/Sp3-binding after induction. These data suggest that contact inhibition of growth and growth arrest caused by histone deacetylase inhibitors probably use the same mechanism to stimulate H-rev107 expression via histone acetylation in NIH3T3 cells and this might contribute to the development of drugs that can induce H-rev107 expression in certain tumors.