MicroRNA-130a (miR-130a) has recently been found to be implicated in many critical processes in various types of human cancer. However, the prognostic value of miR-130a in hepatocellular carcinoma (HCC) remains unclear. In the present study, we investigated the expression of miR-130a in HCC and analyzed its association with clinical features and prognosis of HCC patients. We determined the expression level of miR-130a in 102 cases of paired HCC and adjacent non-tumor tissues by quantitative real-time PCR (qRT-PCR). The qRT-PCR results showed that the miR-130a expression was significantly down-regulated in tumor tissues compared with the adjacent non-tumor tissues (P<0.001). Correlation analysis showed that miR-130a expression was significantly correlated with gender (P=0.008), HBsAg status (P=0.038), tumor size (P=0.003), and tumor-node-metastasis stage (P=0.029). Kaplan-Meier analysis showed that patients with low miR-130a expression had a poorer overall survival than patients with high miR-130a expression (log-rank P=0.007). The multivariate Cox regression analysis indicated that miR-130a expression was an independent prognostic factor for overall survival (hazard ratio 2.217; 95% CI 1.103-4.458; P=0.025). The present study showed for the first time that miR-130a expression was significantly down-regulated in HCC and associated with overall survival of patients with HCC. The present study also provided evidence that miR-130a was an independent prognostic factor and could serve as a potential prognostic biomarker for patients with HCC.