MicroRNAs (miRNAs or miRs) are believed to have great potential for use as molecular targets in the diagnosis and treatment of cancer. In this study, we demonstrate that miR-375 is downregulated in pancreatic carcinoma (PC) tissues and PC cell lines. We found that miR-375 negatively regulates the expression of 3-phosphoinositide-dependent protein kinase 1 (PDK1) by directly targeting the 3'UTR of the PDK1 transcript. To investigate the biological roles and the potential mechanisms of action of miR‑375, we induced either the up- or downregulation of miR-375 expression by transfecting various PC cells with miR-375 mimics or an inhibitor. Our results revealed that the upregulation of miR-375 inhibited cell growth and induced cell apoptosis, while the downregulation of miR-375 with the inhibitor had the opposite effect. In addition, our data demonstrate that miR-375 suppresses the malignant behavior of PC cells through the Akt signaling pathway rather than mitogen-activated protein kinase (MAPK) signaling pathways. Taken together, our findings indicate that targeting miR-375 by a genetic approach may provide a novel strategy for the treatment of PC.