Cellular senescence is a process characterized by permanent cell cycle arrest. It is the consequence of the finite proliferative capacity of normal cells (replicative senescence) and the response to stress and damage from exogenous and endogenous sources. Several years ago it was shown that senescence is an innate tumour suppressive mechanism associated with the activation of oncogenes, which limits the progression of pre-malignant lesions [1]. As a consequence, escape from senescence is a prerequisite for the progression to malignancy. There are three main mechanisms that trigger cellular senescence and that must be quelled in cancer cells: activation of the p53 pathway, upregulation of the CDKN2A locus, and telomere shortening [2]. Genetic and epigenetic aberrations in any or all of these pathways are common marks of all types of human cancer. However, the senescence resistance associated with transformed cells is reversible [3], and senescence-inducing drugs could represent an ideal opportunity to increase the arsenal of anti-cancer weapons [2]. In the present issue of The Journal of Hepatology the work of Menard et al. describes a new example of tumour progression blockage linked to the induction of replicative senescence in a xenograft model of liver cancer [4]. Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world and is characterized by a poor prognosis. In many cases no effective therapy at all can be offered to patients with HCC [5]. Surgical interventions such as tumour ablation or transplantation are restricted to a selected group of patients with very specific clinical features, and non-resectable tumours are resistant to conventional chemotherapy. New strategies such as radiotherapy and gene therapy alone or in combination with cell therapy are at early stages of clinical development [6]. Given the survival benefits of the molecular inhibitor Sorafenib in patients at advanced stages [7] the use of single or combined targeted therapies appears as a promising therapeutic alternative. Recent studies demonstrate the existence of an increasing number of pathways that might be altered by drugs in HCC cells [5]. The molecular profiling of HCC and the identification of patient subclasses according to drug responsiveness will lead to a more per-