MicroRNAs (miRNAs) have been frequently reported to be diagnostic biomarkers and prognostic factors for cancer. The aim of the present study was to evaluate the clinical significance of microRNA-139 (miRNA-139) in hepatocellular carcinoma (HCC). All 31 patients enrolled in the present study had received curative hepatectomy. The objective miRNA was determined using miRNA microarray. The miRNA-139 expression level in cancerous tissue specimens was measured by means of reverse transcription and quantitative polymerase chain reaction, and compared with that in 31 corresponding peritumoral non-cancerous tissues. Plasma miRNA-139 expression was also quantified. The diagnostic value of plasma miRNA-139 for differentiating patients with HCC from the ones with chronic HBV-hepatitis (CH) was analyzed. The miRNA microarray performed in 3 pairs of tissue specimens determined miRNA-139 was downregulated (p=0.017). Compared with plasma of chronic HBV-hepatitis, miRNA-139 was lowly expressed in plasma of HCC patients (p<0.010). ROC analysis of plasma miRNA-139 yielded an AUC of 0.764 (p<0.010) with sensitivity of 80.6% and specificity of 58.1% while differentiating HCC from chronic HBV-hepatitis. The diagnostic power of serum α-fetoprotein (AFP) was also evaluated. The combination of miRNA-139 and AFP improved the differentiating power. Subsequently, 31 HCC patients were divided into the low or high expression group based on plasma miRNA-139 level. Plasma miRNA‑139 expression was correlated with serum AFP (p=0.043), Edmondson-Steiner grading (p=0.038). In addition, there was a significant difference in the 1-year survival rates between the two groups (p=0.023). miRNA‑139 was downregulated in the cancerous tissue and plasma of HCC patients. Plasma miRNA‑139 is a diagnostic biomarker and prognostic factor for HCC.