Abstract: Objective To study the expressive levels of mucin core proteins (MUC1 and MUC5AC) and detect their clinicopathological significances in the benign and malignant lesions of gallbladder. Methods Envision immunohistochemstry for determining the expressions of MUC1 and MUC5AC was used in routine paraffin-embedded sections of surgical resected specimens from gallbladder adenocarcinoma (n=108), peri tumor tissues (n=46), adenoma (n=15), and chronic cholecystitis (n=35). Results The positive rate of MUC1 expression was significantly higher in gallbladder adenocarcinoma than that in peri-tumor tissues (χ^２=16.49，P<0.01), adenoma （χ^２=7.40，P<0.01） and chronic cholecystitis（χ^２=28.57, P<0.01）；The positive rate of MUC5AC expression was significantly lower in gallbladder adenocarcinoma than that in peri tumor tissues (χ^２=12.83，P<0.01), adenoma （χ^２=4.22，P<0.05） and chronic cholecystitis（χ^２=20.25,P<0.01）；The positive cases of MUC1 and/or negative ones of MUC5AC in the benign lesions showed moderately or severe atypical hyperplasia of gallbladder epithelia. The positive rate of MUC1 was significanctly lower in the maximal diameter of mass <2cm, no-metastasis of lymph node, and no invasiveness of regional tissues than those in the maximal diameter of mass ≥2cm, metastasis of lymph node, and invasiveness of regional tissues in gallbladder adenocarcinoma (P<0.05 or P<0.01). The positive rate of MUC5AC was significantly higher in the well-differentiated adenocarcinoma and the maximal diameter of mass <2cm than those in the low differentialed adenocarcinoma and maximal diameter of mass ≥2cm in gallbladder adenocarcinoma (P<0.05 or P<0.01). Conclusion The expression of MUC1 and(or) MUC5AC might be closely related to the carcinogenesis, clinical biological behaviors, and prognosis of gallbladder adenocarcinoma.