Backgrounds:　The　mucosa　of　gallbladder　stimulated　with　gallstones　and　accompanied　with　abnormalities　in　bile　composition,　is　the　origin　of　biliary　disease,　which　could　induce　metaplasia.　simple　hyperplasia,　atypical　hyperplasia　and　even　carcinoma　in　situ　and　invasive　carcinoma　in　gallbladder　mucosa.　Methods:　To　determine　the　disorder　of　the　balance　between　cell　proliferation　and　cell　cycle　or　apoptosis　in　gallbladder　cancer　accompanied　with　gallstones,　removal　of　the　gallbladder　due　to　gallstones　specimens　of　88　cases　were　collected　randomly,　including　a　variety　of　54　cases　for　hyperplasia,　27　cases　for　gallbladder　cancer　and　7　cases　for　normal　gallbladder.　The　expressions　of　key　cell　cycle　factors　were　detected　by　in　situ　hybridization,　immunohistochemistry　and　Western　blot.　Results:　The　expressions　of　CDK4　and　Cyclin　D1　increased　along　with　progression　of　gallbladder　mucosa　hyperplasia;　and　showed　highest　expression　in　cancer　group.　On　the　contrary,　p16　decreased　to　the　lowest　level　in　gallbladder　cancer.　The　increased　apoptotic　index　analyzed　by　TUNEL　assay　rose　along　with　malignant　degree　to　the　highest　level　in　undifferentiated　carcinoma.　Conclusions:　Our　results　suggest　that　changes　of　these　signals　have　effect　on　breaking　the　balance　of　proliferation　and　death　of　gallbladder　epithelial　cells,　even　on　inducing　gallbladder　cancer.　(C)　2011　Elsevier　Inc.　All　rights　reserved.