Liver X receptor (LXR) α and LXRβ are nuclear receptors playing key roles in lipid metabolism, and LXR ligands are attractive drug candidates for metabolic disorders. Here we report the structural development of 4-(1,1,1,3,3,3-hexafluoro-2-hydroxyprop-2-yl)phenylsilane derivatives as LXR agonists bearing silyl functionalities as the hydrophobic pharmacophore, based on the structure of the known sulfonamide LXR agonist T0901317. Most of the synthesized compounds exhibit agonistic activity toward LXRs, but the LXR subtype-selectivity differs depending upon the substituents on the silicon atom. Among them, tri(n-propyl) derivative 12 shows potent LXR-agonistic activity with moderate α subtype-selectivity, while dimethylphenylsilyl derivative 19 shows modest β-selectivity. These results indicate that silanes can serve as an alternative to the sulfonamide moiety of LXR agonists, and are promising structural options for the development of novel subtype-selective LXR agonists.