Although Extracellular vesicles (EVs)in body fluid have been considered to be ideal biomarkers for cancer diagnosis and prognosis, it is still difficult to distinguish EVs derived from tumor tissue and normal tissue. Therefore, the prognostic value of tumor- specific EVs was evaluated through related molecules in pancreatic tumor tissue. NA sequencing data of pancreatic adenocarcinoma(PAAD) were acquired from The Cancer Genome Atlas(TCGA) and International Cancer Genome Consortium(ICGC). EV-related genes in pancreatic cancer were obtained from exoRBase. Protein-protein interaction (PPI) network analysis was used to identify modules related to clinical stage. CIBERSORT was used to assess the abundance of immune and non-immune cells in the tumor microenvironment. A total of 12 PPI modules were identified, and the 3-PPI-MOD was identified based on the randomForest package. The genes of this model are involved in DNA damage and repair and cell membrane-related pathways. The independent external verification cohorts showed that the 3-PPI-MOD can significantly classify patient prognosis. Moreover, compared with the model constructed by pure gene expression, the 3-PPI-MOD showed better prognostic value. The expression of genes in the 3-PPI-MOD had a significant positive correlation with immune cells. Genes related to the hypoxia pathway were significantly enriched in the high-risk tumors predicted by the 3-PPI-MOD. External databases were used to verify the gene expression in the 3-PPI-MOD. The 3-PPI-MOD had satisfactory predictive performance and could be used as a prognostic predictive biomarker for pancreatic cancer.Copyright 2020 The Author(s).