BACKGROUND:: Tumor recurrence in liver transplant recipients greatly affects prognosis of liver transplantation with hepatocellular carcinoma (HCC). How to prevent tumor recurrence has aroused increasing attention. Arsenious acid chemotherapy is considered effective on treating moderate or advanced liver cancer, but its utilization following liver transplantation remains few. OBJECTIVE:: To explore the role of arsenious acid on tumor recurrence in liver transplant patients with primary HCC extending Milan criteria. METHODS:: Twenty-three patients with HCC extending Milan criterion received intravenous arsenious acid chemotherapy after orthotopic liver transplantation (OLT), that is, intravenous injection, 10 mg per day, for 7 successive days, followed by 7-day interval, and a course comprised 4 durations. Each patient treated for 1-4 courses. Other 16 patients did not received chemotherapy served as controls. The difference of patientsʼ survival, tumor recurrence and adverse reaction were compared. RESULTS AND CONCLUSION:: All patients were routinely followed up for 3-32 months. Thirty recipients were presented with tumor recurrence, 16 in the chemotherapy group and 14 in the non-chemotherapy group. Tumor recurred in lung, liver graft and bones in most cases. The total recurrence rate was similar in these two groups, but chemotherapy could delay recurrence after transplantation (P=0.026). There was no significance in 6-month, 1-year survival rate between two groups, but the 2-year survival in the chemotherapy group was higher (P=0.037); 6-month tumor-free survival rates in the two groups had no significance, 1-year and 2-year tumor-free in the chemotherapy group were significantly higher than those in the non-chemotherapy group (P=0.030, 0.023). Intravenous arsenious acid chemotherapy can delay tumor recurrence and prolong survival in liver transplant patients with HCC extending Milan criteria.