In this report, we show that (i) PRL-1 is very frequently amplified and overexpressed in hepatocellular carcinoma; (ii) PRL-1 represses E-cadherin expression associated with enhancing hepatoma cells migration and invasion in concert with activating the PI3K/AKT signaling pathway; (iii) Elevated level of PRL-1 is associated with intravascular metastasis and an independent prognostic factor for poor survival for patients with HCC. Here, AKT1 is linked to hepatocellular carcinoma.