The oxysterol nuclear receptors, LXR${alpha}$ (liver X receptor ${alpha}$; NR1H3) and LXR${eta}$ (NR1H2), coordinately regulate the expression of genes involved in lipid metabolism, anti-inflammation, and cholesterol transport. Previous studies have demonstrated that ligands of LXR${alpha}$ are important in the maintenance of the normal epidermal barrier function and keratinocyte differentiation. In this study, we examined whether LXR${alpha}$ and its ligands regulate lipid synthesis in HaCaT cells, a spontaneously transformed human keratinocyte cell line. When HaCaT cells were treated with the LXR${alpha}$ ligand TO901317, lipid droplets accumulated in the majority of cells, which were stained by Oil Red O. A luciferase reporter construct containing the LXR response element was activated about fourfold in HaCaT cells by TO901317 treatment, suggesting that LXR has a role in lipid synthesis in these cells. The expression of LXR${alpha}$ target genes, such as those encoding sterol regulatory binding protein and fatty acid synthase, were induced time dependently by TO901317, as measured by RT-PCR and western blotting. The expression of PPAR-${alpha}$, -${eta}$, and -${gamma}$ which regulate lipid metabolism, was also increased by TO901317 treatment. In contrast, TO901317 reduced the lipopolysaccharide-induced expression of cyclooxygenase 2 and inducible nitric oxide synthase in HaCaT cells. These results indicate that LXR${alpha}$ activation leads to lipogenesis in keratinocytes, which may enhance the epidermal barrier function of the skin.