Background: Hepatocellular carcinoma (HCC) is currently the fifth most common solid tumor worldwide and the third leading cause of cancer-related death. Large tumor size appear to be a major obstacle for RFA, so attempts to increase the volume of coagulation by injecting hypertonic saline before,during or both before and during RFA application.Trans arterial chemoembolization(TACE) combines the effect of targeted chemotherapy with that of ischemic necrosis induced by arterial embolization and eliminate heat loss mediated by tissue perfusion if combined with RFA.For nodular, HCC larger than 5cm combined therapy of RFA and TACE has an effective therapeutic effect on nodular lesion but larger infilterative lesions are still a challenging problem. . Aim of the work: The aim of this study was to compare the efficacy of hypertonic saline enhanced radiofrequencye and chemoembolization sequential radiofrequency in treatment of medium and large nodular hepatocellular carcinoma Patients and methods: This prospective study was conducted on 40 patients with 40 focal HCCs between 2008 and 2011. They were divided into 2 groups, the first group included 20 patient underwent hypertonic saline enhanced radiofrequency(RFA+HS), the second group included 20 patients underwent chemoembolization followed by RFA. Effectiveness was compared between medium (3.1-5.0 cm) and large (5.1-7.0 cm) HCC by triphasic CT after one month and 6 months and cases with partial ablation underwent additional sessions of the same technique.Complete laboratory investigations were done before and after the procedures and complications were recorded. Survival analysis was conducted for 6 month duration following the last session of ablation. Results: After one month:The triphasic spiral CT done one month after the procedure in both group showed that, 85% of patients (34 patients) had complete ablation in both groups (17 patients in each group) while 15% (6 patients) had partial ablation (3 patients in each group), 4 patients were re-ablated using the same technique and 2 patients underwent no further therapy due to development of PV thrombosis. As regard the diameter of ablated lesions, 20/21 (95%) of medium HCC lesions and 14/19 (73%) of large HCC lesions were successfully ablated. In RFA+S group 12/13 (92%) of medium HCC were successfully ablated, and 5/7 (71%) of large HCC lesions were ablated. In the TACE+RFA group 8/8 (100%) medium HCC were ablated and (9/12) (75%) of large lesions were ablated successfully.After six monthsIn 29 patients (78.4%) showed maintained ablation (73.7% in group 1 and 83.3% in group 2) (p=0.86) while 8 patients (21.6%) showed residual enhancement.Fever,abdominal pain and ascites were the main complications with 3 cases developed haematemesis caused by rupture oesophageal varices.Conclusions: The results of this study show that RFA+HS and TACE+RFA are safe and equally effective treatment for HCCs 3.1 up to 7.0 cm in diameter, even for patients with cirrhosis with suboptimal hepatic function. However, studies with long-term follow-up data are awaited to further clarify their role in the treatment of this group of patients, and prospective randomized trials are needed to compare its effectiveness with that of other currently available treatments for HCC