The present study aimed to analyze the role and mechanism of miR-15b in hepatocellular carcinoma (HCC) after curative hepatectomy. Tissue samples from 13 patients with HCC who were operated on at the Chinese PLA General Hospital from March 2014 to May 2014 were collected. A consecutive 156 untreated patients with HCC who received curative hepatectomy at the Chinese PLA General Hospital (Beijing, China) from May 2008 to March 2009 were enrolled, and their corresponding para-tumoral and normal tissue samples were acquired. Subsequently, anti-miR-15b (inhibitor) was transfected into human HCC HepG2 cells. It was observed that high expression of miR-15b promoted cell proliferation of the HCC cells, while low expression of miR-15b suppressed cell growth and induced the apoptosis of HepG2 cells. It was found that overall survival of the patients with low miR-15b was increased, compared with the overall survival of the patients with high miR-15b expression. In addition, low expression of miR-15b suppressed the growth of HepG2 cells by suppression of transforming growth factor-β (TGF-β), TβRI and Smad2 protein expression. Meanwhile, low expression of miR-15b significantly activated Bax protein expression and caspase-3 activity in the HepG2 cells. The study results revealed that high expression of miR-15b could predict the poor prognosis of hepatocellular carcinoma after curative hepatectomy through TGF-β/TβRI-Smad2-cyclin D1/Bax.