Liver failure (LF) is a severe life-threatening condition, and is a dramatic clinical syndrome with massive necrosis of liver cells, and liver transplantation is the only available therapeutic option for patients suffering with this condition. However, lack of donors, surgical complications, rejection, and high cost are serious problems. Since current therapeutic options for LF that is usually with extremely poor prognosis are still limited, recent studies indicate that mesenchymal stem cells (MSCs), due to their function in immune modulation and liver-damage repair, are of great therapeutic potential for this disease. Previous study showed that bone marrow derived mesenchymal stem cells (BM-MSCs) replace hepatocytes in injured liver, and effectively rescue experimental liver failure and contribute to liver regeneration.The purpose of this study is to investigate the safety and initial efficacy of human umbilical cord MSC (UC-MSCs) treatment for patients with LF. In this study, MSCs were isolated from umbilical cord and generated in appropriate growth medium. 50 LF patients with LF received i.v. transfusion of 0.5-1.0×106 cells/kg of MSCs as the treated group and other 20 LF patients with LF were transfused with placebo without MSCs as control group. All 70 of them received the routine management for liver failure. During the 2-year follow up, the evaluation of safty and efficacy will be undergone to help to establish innovative cell-based therapies for the treatment of diseases.