In the present study, we monitored the changes in caspase 3/8 in TRAIL-sensitive and TRAIL-resistant hepatocellular carcinoma cells, and searched for candidate miRNAs that might target to regulate caspase 3/8; the expression, role and mechanism of candidate miRNAs in regulating TRAIL resistance of hepatocellular carcinoma cell was then investigated; in addition, we investigated whether CASC2 affected TRAIL resistance of tumor cell through miRNAs. This evidence concerns the gene TNFSF10 and hepatocellular carcinoma.