Abstract: Objective To analyze the differential expression and clinical significance of mucin 4 （MUC4） in pancreatic intraepithelial neoplasias（PanINs）and pancreatic ductal adenocarcinoma （PDAC）. MethodsWe collected 85 cases of paraffin of pancreatic tissue specimens from Affiliated Changzheng Hospital of the Second Military Medical University from 2009-03-01 to 2011-12-31. Immunohistochemical SP method was used to examine the expression of MUC4 in 48 normal pancreatic duct （NP） tissues，17 PanINs tissues and 20 PDAC tissues. The correlation of MUC4 expression with clinicopathological characteristics and prognosis of PDAC patients was analyzed. Results MUC4 was not expressed in NP；MUC4 expression gradually increased with the progression of pancreatic tissue. The positive expression rates of MUC4 in NP，PanIN-1， PanIN-2，PanIN-3 and PDAC were 0， 17.4%， 52.6%， 84.6% and 90.0%， respectively； The immunohistochemical scores of MUC4 expression in NP， PanIN-1， PanIN-2， PanIN-3 and PDAC groups were 0, 1.30±0.89, 2.58±1.76, 4.54±1.64 and 7.68±2.34, with statistic significance among groups （P＜0.001）. The expression level of MUC4 was associated with neural invasion （P=0.028）， lymph node metastasis （P=0.020） and CA19-9 level （P=0.028） in PDAC. The median overall survival（OS） of PDAC patients was 17.0 months（95%CI：14.809-19.191 months）；The median OS of MUC4 high expression group （immunohistochemical score≥8.8） and low expression group （immunohistochemical score ＜8.8） were 13.0 months （95%CI：7.456-18.544 months） and 20.0 months （95%CI：15.521-24.479 months）， with statistic significance （P=0.003）. Conclusion MUC4 perhaps participates in the PDAC occurrence and development. MUC4 expression may be an early event in the evolution of PDAC. MUC4 high expression probably affects both invasion and metastasis of PDAC，and probably predicts poor prognosis.