Oncolytic adenoviruses are promising agents for cancer therapy and providing a new therapeutic strategy for pancreatic ductal adenocarcinoma (PDAC) gene therapy. However, the challenges associated with the therapeutic effect of oncolytic adenovirus alone include security of virus vector and screening of effective antitumor gene. In this study, a novel oncolytic adenovirus CD55-ST13-TRAIL was constructed featured with CEA promoter to control E1A, and E1B 55 kDa gene deletion in which dual therapeutic gene ST13 and TRAIL was inserted. ST13, firstly as a colorectal cancer suppressor gene, was also lower expression in PDAC than in tumor-adjacent tissues, which was associated with poor prognosis of PDAC patients. In vitro studies showed that CD55-ST13-TRAIL can efficiently proliferate and promote the expression of ST13 and TRAIL in CEA positive pancreatic cancer cells. Moreover, CD55-ST13-TRAIL has a synergic cell-killing effect compared with CD55-ST13 alone or CD55-TRAIL alone, and the inhibition of PDAC cell metastasis and promotion of apoptosis by triggering EMT and apoptotic pathways in PDAC cells. Further xenograft experiments in mice model indicated that CD55-ST13-TRAIL significantly inhibited tumor growth and improved the survival rates of xenograft animal. The findings demonstrated that the oncolytic virotherapy under the control of CEA promoter enables the treatment safety and efficiency to PDAC, which makes it a promising candidate for the treatment of metastatic diseases.