MicroRNAs (miRNA) have recently been implicated in carcinogenesis and tumor progression. Hepatocellular carcinoma (HCC) is well known for frequent relapses following curative resection. We attempted to identify the miRNAs associated with HCC recurrence. We analyzed miRNA expression profiles in 25 pairs of HCC and adjacent non-tumor liver tissues from HCC patients using miRNA microarray. Out of 449 miRNAs assayed, we identified seven miRNAs associated with HCC recurrence. In particular, the highest ranked miR-15b was negatively correlated with recurrence. MiR-15b inhibitor transfection increased HCC cell proliferation and inhibited TRAIL-induced apoptosis, while miR-15b precursor transfection decreased proliferation and enhanced apoptosis. Bcl-w was identified as a target molecule regulated by miR-15b. These results indicate that miR-15b expression in HCC tissues may predict a low risk of HCC recurrence. In addition, the modulation of miR-15b expression may be useful as an apoptosis-sensitizing strategy for HCC treatment.