MicroRNAs (miRNAs or miRs) have been shown to regulate hepatocellular carcinoma (HCC) metastasis. In the present study, we focused on the functions of miR-1271 in HCC metastasis. The downregulation of miR-1271 was found to be associated with to venous infiltration, an advanced TNM stage (III+IV stage) and a shorter survival time. Our in vitro and in vivo data demonstrated that miR-1271 prevented HCC cell migration and invasion, as well as the formation of lung metastatic clusters. In addition, miR-1271 was demonstrated to markedly inhibit the epithelial-mesenchymal transition (EMT) of HCC cells. Importantly, protein tyrosine phosphatase type IVA member 1 (PTP4A1) was identified as a direct downstream target of miR-1271 in HCC. Furthermore, we confirmed that the phosphorylation of c-Src at Tyr416 mediated by PTP4A1 was a potential anti-HCC mechanism of action of miR-1271. On the whole, our data indicate that miR-1271 inhibits HCC metastasis by targeting the PTP4A1/c-Src signaling pathway and may serve as a prospective cancer therapeutic target for HCC.