Dysregulation of microRNA (miRNA) expression in multiple cancers and their vital roles in malignant cancer progression are well investigated. The purpose of this study was to explore the biological roles of miR-876-3p in pancreatic cancer. We used genome-wide gene expression analysis in clinical pancreatic adenocarcinoma samples to identify miR-876-3p down-regulated in pancreatic cancer. We then collected 22 pairs of pancreatic cancer and the corresponding non-cancerous tissues to determine miR-876-3p level, and confirmed that miR-876-3p was significantly down-regulated in pancreatic cancer. Furthermore, functional analysis suggested that overexpression of miR-876-3p suppressed cell growth and aggressively increased cells apoptosis in BXPC-3 and PANC-1 cells, whereas down-regulation led to the opposite results. We identified Jagged2 (JAG2) as a direct target of miR-876-3p, and an inverse correlation between miR-876-3p and JAG2 was observed in pancreatic adenocarcinoma. Moreover, miR-876-3p and a JAG2 siRNA were co-transfected into both PANC-1 and BXPC-3 cells to explore the mechanism of miR-876-3p and JAG2 on pancreatic adenocarcinoma tumorigenesis. Down-regulation of JAG2 inhibited the overexpression effects of miR-876-3p, and up-regulation of JAG2 reversed the effects of overexpressed miR-876-3p. Cumulatively, these results revealed a significant role of the miR-876-3p/JAG2 axis in suppressing pancreatic adenocarcinoma cell growth and aggressiveness.