Introduction Hepatocellular carcinoma (HCC) is a major health problem, accounting for more than 626,000 new cases per year worldwide. It is the third highest cause of cancer-related death globally. In the west, the disease is diagnosed in 30 to 40% of all patients at early stages and is amenable to potentially curative treatments, such as surgical therapies (resection and liver transplantation) and locoregional procedures (radio-frequency ablation). There are no clear epidemiological studies in the Kingdom of Saudi Arabia that gives the real incidence of HCC in Saudi population, however the Saudi Cancer registration have labelled it as among the top five cancers in the country. Sorafenib has emerged as the treatment of choice in the treatment of advanced HCC and has demonstrated an anti-angiogenic and anti-proliferative effect. It is a kinase inhibitor that decreases tumor cell proliferation in Vitro. Sorafenib has been shown to inhibit multiple intracellular (CRAF, BRAF, and mutant BRAF) and cell surface kinases (KIT, FLT-3, RET, VEGFR-1, VEGFR-2, VEGFR-3 and PDGFR-B). Several of these kinases are thought to be involved in tumor cell signaling, angiogenesis and apoptosis. In a phase 3 international, multi-center, randomised, doubleblind, placebo-controlled trial in patients with unresectable hepatocellualr carcinoma Sorafenib showed a statistically significant advantage over placebo for overall survival (HR: 0.69, p=0.00058). Final analysis of time to tumor progression also was significantly longer in the Protocol number: 1.0 dated 01Aug2013 Short title: HCC - Sorafenib study Confidential Page 11 The Long-Term Comprehensive National Plan for Science, Technology and Innovation Sorafenib arm. This benefit was calculated in months because of the quick emergence of resistance in many patients. Therefore, individualizing the treatment to patients with most expected response and avoiding it in patients with resistant cancers has stimulated this research to evaluate why some patients develop resistance to this therapy.