Despite　the　fact　that　the　majority　of　gallstones　formed　in　the　gallbladder　are　mainly　composed　of　cholesterol,　as　they　are　formed　from　cholesterol-supersaturated　bile,　and　hypercholesterolemia　is　a　common　metabolic　disorder,　which　is　closely　related　to　cardiac,　hepatic,　renal　and　other　oxidative　damage　inflammation　and　necrosis,　there　is　still　no　consensus　regarding　the　contribution　of　blood　serum　lipids　in　the　pathogenesis　of　gallbladder　stone　disease　(GSD).　This　study　aimed　to　investigate　the　relationship　between　hypercholesterolemia　and　the　risk　of　new-onset　asymptomatic　GSD,　and　to　determine　the　prevalence　of　factors　associated　with　new-onset　asymptomatic　GSD　in　patients　with　hypercholesterolemia.In　this　study,　927　Chinese　patients　with　new-onset　asymptomatic　gallstone　disease　and　845　healthy　controls　were　enrolled　starting　from　August　2012.　Patients　were　matched　for　age,　gender,　race,　occupation,　systolic　blood　pressure,　diastolic　blood　pressure,　and　fasting　blood　glucose　levels　(FBG).　Body　mass　index　(BMI),　nonalcoholic　fatty　liver　disease　(NAFLD)　and　serum　lipids　indexes　were　compared　and　the　relationships　between　BMI,　blood　lipid　and　gallbladder　stone　hazards　were　examined　by　logistic　multivariate　regression　models.The　result　showed　a　significantly　higher　morbidity　with　GSD　in　hypercholesterolemia　than　non-hypercholesterolemia　patients　(Χ2　=　17.211,　P　＜　0.001).　Of　hypercholesterolemia　patients,　low　density　lipoprotein　(OR　=　1.493,　P　=　0.029)　and　NAFLD　(OR　=　2.723,　P　=　0.022)　were　significant　risk　factors　for　GSD,　while　being　male　(OR　=　0.244,　P　=　0.033),　weight　(OR　=　0.961,　P　=　0.022),　high　density　lipoprotein　(OR　=　0.305,　P　＜　0.001),　and　FBG　(OR　=　0.687,　P　=　0.034)　were　significantly　negatively　correlated　with　GSD　in　univariate　analysis.　Multivariate　logistic　regression　indicated　weakly　positive　correlations　with　NAFLD　(OR　=　3.284,　P　=　0.054),　and　significant　negative　correlations　with　weight　(OR　=　0.930,　P　=　0.018),　HDL-c　(OR　=　0.144,　P　＜　0.001),　and　GSD.Hypercholesterolemia　acts　as　an　independent　risk　factor　for　new-onset　asymptomatic　GSD,　while　obesity　and　NAFLD　are　synergistic　factors.　Interestingly,　it　is　first　reported　that　elevated　weight　was　inversely　associated　with　GSD　in　patients　with　hypercholesterolemia.　The　results　of　this　study　suggest　that　effective　control　of　hyperlipidemia　is　of　greater　significance　than　weight　loss,　which　might　make　the　situation　worse,　in　the　prevention　of　GSD　in　obese　patients　with　hyperlipidemia.