We explored the ability of a long non-coding RNA H19, to influence oxidative stress (OS) and chemotherapy resistance of CD133 + cancer stem cells via the MAPK/ERK signaling pathway in HCC. HCC tissues with corresponding adjacent normal tissues were collected. CD133 + HuH7 cells were sorted and assigned into five groups. Quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting were performed to determine expression levels mRNAs and proteins. Levels of reactive oxygen species (ROS) and malonaldehyde (MDA), and activity of superoxide dismutase (SOD) were measured. Cell viability was analyzed by MTT assay and cell apoptosis by flow cytometry. Compared with adjacent normal tissues, the H19 expression level was higher and MAPK and ERK protein levels were lower in HCC tissues. Compared with the blank group, in the pcDNA-H19 group, H19 expression level, MAPK and ERK protein levels, MDR1 and GST-pi expression levels were increased, ROS and MDA levels were decreased, SOD activity was weakened, cell viability was promoted, and cell apoptosis was inhibited; in the siH19 group, H19 expression level, MAPK and ERK protein levels, MDR1 and GST-pi expression levels were reduced, ROS and MDA levels were elevated, SOD activity was enhanced, cell viability was inhibited, and cell apoptosis was promoted. There was no significant difference among blank, NC and pcDNA-H19 + PD98059 groups. The study provides evidence that downregulation of H19 may induce OS and reverse chemotherapy resistance of CD133 + cancer stem cells by blocking the MAPK/ERK signaling pathway in HCC. (C) 2018 Elsevier Inc. All rights reserved.