Abstract: The etiology of Cholesterol gallstone is complexed which includes changing of biliary lipid secretion, cholesterol crystal, immune reaction in the tissues of the gallbladder, formation of mucin, defection of gallbladder motility and so on. One of the therapeutic approaches to cholesterol gallstones is reducing bile secretion and absorption of cholesterol in intestinal. The expression level of Niemann - Pick C1 proteins has a dual role to the incidence of cholesterol gallstones. In this paper, we reviewed the progress of targeting NPC1L1 protein as a treatment of cholesterol gallstones.