Consistent with previous findings by Ma et al. 16, 17, our present study showed that in hypoxic HCC cells, YAP was predominantly localized in the nucleus, thus exerting its function, i.e., transactivating the target genes CTGF, Cry61 and others, which may promote hypoxic resistance towards sorafenib (Fig. 1). This evidence concerns the gene CCN2 and hepatocellular carcinoma.