Increasing evidence indicates that dysregulation of microRNAs (miRNAs) contributes to tumorigenesis. MicroRNA-340 (miR-340) is downregulated in several types of cancer. However, the functional mechanism of miR-340 in hepatocellular carcinoma (HCC) remains unclear. Here, we showed that miR-340 was significantly downregulated in HCC tissues and cell lines. Gain-of-function experiments demonstrated that miR-340 overexpression inhibited HCC cell proliferation, migration, and invasion in vitro, and suppressed tumor growth in vivo. Janus kinase 1 (JAK1) was identified as a direct target of miR-340 in HCC cells. Ectopic expression of JAK1 reversed the inhibitory effects of miR-340. Further investigations showed that miR-340 dramatically inhibited the expression of signal transducer and activator of transcription (STAT) 3 downstream molecules including Bcl-2, cyclin D1, and matrix metalloprotease (MMP)-2. The present findings indicated that miR-340 suppressed HCC cell proliferation and invasion by regulating the JAK1/STAT3 pathway, suggesting its potential as a novel therapeutic target for HCC. (C) 2016 Elsevier Inc. All rights reserved.