Liver-X-Receptor alpha (LXR-α) that belongs to nuclear receptor/transcriptional factor family has been recognized to play crucial role in the regulation of lipid metabolism and inflammation. Consequently, the present study was addressed to explore the functional genomics of LXR-α within human blood immunomodulatory cells. The results of such a study, which involved LXR-α gene silencing through siRNA approach, revealed that: (a) the mRNA expression of genes coding for IL-8, IL-4, CX3CR1, LDLR, hTERT and c-myc was significantly elevated in response to LXR-α gene silencing whereas mRNA expression of genes coding for PPARs(α, γ), CD36 and Dicer could not be detected; (b) the expression of Receptor C k protein remained unaffected; (c) the mRNA expression of IFN-γ gene was down regulated in LXR-α knockdown cells. Based upon these results we propose that LXR-α gene plays a crucial role in the regulation of innate immunity at the genomic level.