Endoplasmic reticulum (ER) stress plays an important role in hepatocyte degeneration, especially in patients with chronic liver injury. Protein kinase R-like endoplasmic reticulum kinase (PERK) is a key molecule in ER stress. PERK may contribute to apoptotic cell death in HCC, however the details of the mechanism are not clear. In this study, we identified PERK-associated molecules using transcriptome analysis. We modulated PERK expression using a plasmid, tunicamycin and siRNA against PERK, and then confirmed the target gene expression with real-time PCR and Northern blotting. We further analyzed the apoptotic function. Transcriptome analysis revealed that expression of the RNA component of mitochondrial RNA processing endoribonuclease (RMRP), which is a long noncoding RNA, was strongly correlated with the function of PERK. The expression of RMRP was correlated with the expression of PERK in experiments with the siRNA and PERK plasmid in both HCC cell lines and human HCC tissue. Furthermore, RMRP downregulation induced apoptotic cell death. RMRP is downregulated by PERK, which induces apoptosis in HCC. RMRP could be a new therapeutic target to regulate HCC in patients with chronic liver diseases associated with ER stress.