Gallstone disease is a complex disorder that can be caused by environmental influences, common genetic factors and their interactions. Three major pathogenic abnormalities are considered to involve in gallstone formation: cholesterol supersaturation in bile, precipitation and nucleation of excess cholesterol, and gallbladder hypomotility, while, mucin takes part in the cholesterol nucleation process. Up to date, more than 20 mucin genes have been reported, 9 of them are identified at the mRNA and/or protein level in native gallbladder and its associated diseases. In the gallbladder, mucin is essential for best protection against detergent effect of high concentration of bile acids. Over the past decade, the properties, expressions and functions of the gallbladder mucins are delineated in animal and human studies. Alteration expressions of mucins are thought to response during the pathogenesis of gallstone formation. Moreover, recent genetic association study demonstrated mucin gene polymorphisms may also influence susceptibility to gallstone disease. This review is not to provide a complete coverage of all the aspects of mucin glycoproteins, but focus on the role and expression of mucins involve in the regulation of cholelithogenesis.