Abstract Background: Little is known about the effect of esophageal varices on the outcome of radiofrequency (RF) ablation in patients with hepatocellular carcinoma (HCC). Aim of Study: To determine the therapeutic efficacy of radiofrequency ablation of hepatocellular carcinoma associated with esophageal varices, and the important risk factors that affect the outcome. Patients and Methods: 121 of 168 patients with portal hypertension had esophgeal varices, underwent RF ablation as a treatment for a single HCC (9 5cm). Therapeutic efficacy was evaluated. Logistic regression analyses of risk factors for occurrence of complication and multivariate cox-regression analyses for overall survival were detected. Results: Patients with HCC and esophageal varices had a complete ablation rate of 88.4%. Portal vein thrombosis was the most type of complication. By univariate analysis, thrombocytopenia (p=0.032) was independent risk factor of complications. By multivariate analysis, left lobe location of HCC (p=0.015) was independent risk factor of complications and subcapsular location of HCC (p=0.019), was independent prognostic factors for survival. Conclusion: This current study has proven that patients with portal hypertension and esophageal varices can tolerate RF ablation of HCC. Dealing caution as regard correction of thrombocytopenia and professionally as regard location of HCC, we can improve the outcome of RF ablation.