An microRNA (miRNA) signature to predict the clinical outcome of pancreatic adenocarcinoma (PAAD) is still lacking. In the current study, we aimed at identifying and evaluating a prognostic miRNA signature for patients with PAAD. The miRNA expression profile and the clinical information regarding patients with PAAD were recruited from The Cancer Genome Atlas database. Differentially expressed miRNAs were identified between normal and tumor samples. By means of survival analysis, a 4‐miRNA signature for predicting patients' with PAAD overall survival (OS) was constructed. Receiver operating characteristic (ROC) analysis was applied to determine the efficiency of survival prediction. Furthermore, the biological function of the predicted miRNAs was evaluated using a bioinformatics approach. Four (hsa‐mir‐126, hsa‐mir‐3613, hsa‐mir‐424, and hsa‐mir‐4772) out of 17 differentially expressed miRNAs were associated to the OS of patients with PAAD. Moreover, the area under the curve (AUC) of the constructed 4‐miRNA signature associated to patients' with PAAD 2‐year survival was 0.789. The multivariate Cox's proportional hazards regression model suggested that this 4‐miRNA signature was an independent prognostic factor of other clinical parameters in patients with PAAD. Further pathway enrichment analyses revealed that the miRNAs in the 4‐miRNA signature might regulate genes that affect focal adhesion, Wnt signaling pathway, and PI3K‐Akt signaling pathway. Thus, these findings indicated that the 4‐miRNA signature might be an effective independent prognostic biomarker in the prediction of PAAD patients' survival.