Liver cancer represents the fourth leading cause of cancer related mortality worldwide. Despite being a curative treatment, only 20% of hepatocellular carcinoma patients receive surgical treatment. Selection criteria have been used to select HCC candidate with best oncological outcome for liver transplantation long time ago depending on the tumoral morphological features. While in fact, HCC is a kinetic tumor and its biological behavior is difficult to estimate. Judging tumor oncology only by morphology might be misleading. On the other hand, HCC is a double prognostic tumor which develops usually on regenerating premalignant liver background. Thereafter the evaluation of the oncological outcome is multifactorial. The role of conformal radiotherapy as neoadjuvant treatment before liver transplantation has been illustrated by our work to be capable of achieving equivalent oncological outcome to other traditional locoregional therapies in a special subgroup of patients who is offered only systemic treatment, according to the stage-based guidelines, with expected 10 months survival. Also, we illustrated the suboptimal performance of our traditional prognostic model on selecting non-HCV induced HCC patient. This problem might grow in the near future with the documented drop of HCV and HCV induce HCC prevalence owing to the new directly acting antiviral agents. In addition, we conducted a genetic analysis to evaluate the molecular biological role in prediction of post-transplant tumor recurrence in matched cohort regarding tumor morphology and underlying liver function and pathology. Finally, we evaluated the predictive values of different prognostic models at different stages of treatment for estimating post-transplant tumor recurrence. Expansion of the selection criteria for transplantation in HCC is proved to be achievable with satisfactory oncological results but prognostics of HCC are multifactorial including tumoral morphological, genetic factors, in addition to the underlying cirrhotic background and therefore, all these elements should be considered for better decision making