Increasing CBX4 levels in HCC cells enhances HIF1α-dependent YAP1 nuclear translocation and induces sorafenib resistance, but blocking CBX4 and YAP1 with the CBX4 inhibitor UNC3866 and the YAP1 inhibitor CA3 significantly suppresses tumour cell growth and CSC properties, particularly in SR cells. Here, CBX4 is linked to neoplasm.