With the wealth of findings outlined in this review, one might wonder about the future research directions, particularly at these three levels: (1) biomarkers that can help in the early detection of HCC or recurrence and are based on the MDM2-p53 interaction; (2) studies that correlate tumor characteristics including MDM2-p53 and survival pattern of patients with HCC; and (3) therapeutic interventions that are directed at MDM2 inhibition, thereby restoring p53 function or stimulating p53 functions. Here, MDM2 is linked to neoplasm.