The mounting evidence suggests that CSCs are particularly resistant to chemotherapy,44 and cells with sorafenib resistance maintain their CSC properties.27 Our previous findings indicated that YAP1 plays a critical role in CSC self-renewal and tumour formation and that suppressing YAP1 could be an effective way to prevent the maintenance of CSCs.21 In this study, we propose that targeting the CBX4-mediated YAP1 activity could be viable in treating CSCs and might be a novel strategy for SR HCC. Here, YAP1 is linked to hepatocellular carcinoma.