To determine the safety, feasibility and therapeutic effect of in vitro-expanded autologous bone marrow-derived liver stem cells (BMDLSC) transplantation in cirrhotic patients following chronic hepatitis B virus infection. Twelve patients with post-hepatitic cirrhosis and portal hypertension who required splenectomy with periesophagogastric devascularization were included and were divided into two groups. Group I included six patients who received autologous BMDLSC infusion via the hepatic artery after in vitro expansion for 7 days. Group II (control group) included six patients who received normal saline infusion via the same route during splenectomy with periesophagogastric devascularization. The therapeutic effects were compared 3 months later. Patients in Group I were followed-up for 24 months after transplantation. There were no adverse effects during short- and long-term follow-ups. Three months after the operation, patients who received BMDLSC infusion showed better hepatic function than those who received saline infusion (p<0.05). Patients in Group I showed stable liver function parameters with no complications during the 24-month follow-up period. Transplantation of in vitro-expanded autologous BMDLSC via the hepatic artery is a safe and effective treatment for decompensated liver cirrhosis.