MDM2 is an oncogene originally identified as being amplified on double-minute chromosomes in transformed mouse fibroblasts.23 MDM2 has been shown to have an important role in cancers, stem cells and cancer stem cells.24, 25, 26 In addition, MDM2 is a member of the RING finger family of E3 ubiquitin ligases and negatively regulates the tumor suppressor protein p53.27 However, recent studies have shown that MDM2 also exerts p53-independent activities.28 In our model, MDM2 was shown to be necessary for HBx to regulate the stem-like characteristics of OV6+ liver CSCs in a p53-independent manner. This evidence concerns the gene MDM2 and cancer.