Objective To investigate the clinical value of sorafenib in preventing tumor recurrence in patients with hepatocellular carcinoma (HCC) after liver transplantation (LT). Methods A total of 41 patients with HCC beyond University of California, San Francisco (UCSF) criteria receiving LT in Department of Hepatobiliary Pancreatic Surgery, People's Hospital of Zhengzhou from March 2010 to July 2012 were enrolled in this prospective study. The informed consents of all patients were obtained and the ethical committee approval was received. There were 35 males and 6 females with age ranging from 34 to 61 years old and the median age of 49 years old. According to whether the patients chose sorafenib for  Objective To investigate the clinical value of sorafenib in preventing tumor recurrence in patients with hepatocellular carcinoma (HCC) after liver transplantation (LT). Methods A total of 41 patients with HCC beyond University of California, San Francisco (UCSF) criteria receiving LT in Department of Hepatobiliary Pancreatic Surgery, People's Hospital of Zhengzhou from March 2010 to July 2012 were enrolled in this prospective study. The informed consents of all patients were obtained and the ethical committee approval was received. There were 35 males and 6 females with age ranging from 34 to 61 years old and the median age of 49 years old. According to whether the patients chose sorafenib for treatment after operation, they were divided into sorafenib group (n=9) and control group (n=32). Patients were treated with sorafenib orally (400 mg) twice daily in sorafenib group, and half dose (200 mg) was given twice daily when the patients were intolerant to the adverse reactions. In control group, patients did not take sorafenib or changed to take sorafenib after tumor recurrence. Patients received follow-up after operation, and tumor recurrence and survival were recorded during the follow-up. The tumor recurrence rates after operation of two groups were compared using Chi-squane test. The postoperative 1-, 2-year disease-free survival and cumulative survival rates were compared using Kaplan-Meier method and Log-rank test. Results The tumor recurrence rate was 3/9 in sorafenib group including 2 cases of taking half dose sorafenib. The tumor recurrence rate was 47%(15/32) in control group including 3 cases with liver metastasis underwent radiofrequency ablation, 2 cases with pulmonary metastases underwent radiation therapy, 2 cases with pulmonary metastases took sorafenib, the other 8 cases with multiple metastases received no treatments. No signiifcant difference was observed in tumor recurrence rates between two groups (χ2=0.523, P>0.05). No death was observed in sorafenib group, while in control group, 12 cases died of tumor recurrence or metastasis. The postoperative 2-year disease-free survival rates were 67%, 53%in sorafenib group and control group respectively and no signiifcant difference was observed (χ2=2.226, P>0.05). The postoperative 2-year cumulative survival rates were 100%, 63%in sorafenib group and control group respectively and signiifcant difference was observed (χ2=5.126, P<0.05). Conclusion For patients with HCC beyond UCSF criteria after LT, sorafenib can improve the 2-year cumulative survival rate and has a certain value in preventing tumor recurrence after operation.