Hepatocellular carcinoma (HCC) is the leading cause of cancer-related mortality worldwide. MiR-371 recently emerged as an important regulator in tumorigenesis, and might serve as a biomarker for malignant tumors. We transfected miR-371 or its inhibitor in two human HCC cell lines, and used 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, soft agar colony formation and transwell migration assays to evaluate its effect on cell proliferation, migration and invasion. We found miR-371 was positively correlated with HCC metastasis and poor prognosis of the inflicted patients, and high expression of miR-371 promoted, whereas low level of miR-371 depressed cell proliferation and invasion. We found PTEN to be a direct target of miR-371. Overexpression or knockdown of PTEN exhibited opposite effect compared to those of miR-371 on cell proliferation and migration. Our study demonstrates that miR-371 promotes proliferation and metastasis in HCC by targeting PTEN.