Jmjd6 is a conserved nuclear protein which possesses histone arginine demethylation and lysyl hydroxylase activity. Previous studies have revealed that Jmjd6 is essential for cell differentiation and embryo development. However, the role of Jmjd6 in mammalian ES cell identity and reprogramming has been unclear. Here we report that depletion of Jmjd6 not only results in downregulation of pluripotency genes but also is implicated in apoptosis, glycolysis, cell cycle and protein hydroxylation. We also revealed the reduction of BrdU incorporation in Jmjd6 depleted cells. Reprogramming efficiency of MEFs can be enhanced with Jmjd6 overexpression while the efficiency was reduced upon Jmjd6 depletion. Together, these results suggest that Jmjd6 can regulate ES cell homeostasis and enhance somatic cell reprogramming.