OBJECTIVE To investigate the effect of lamivudine, interferon alpha and oxymatrine treatment for surviving hepatic failure patients with hepatitis B. METHODS 200 hepatitis B patients, including 100 subacute or acute-on-chronic hepatic failure survivals (group A), and 100 chronic (group B, n=100) hepatic failure survivals, were enrolled in this study. Patients in group A received interferon alpha (n=35), lamivudine (n=33) , or combinational lamivudine and oxymatrine (n=32) therapy for six months; Patients in group B received lamivudine (n=49), or combinational lamivudine and oxymatrine (n=51) therapy for six months, respectively. After the treatment, all patients were followed-up for six months. RESULTS At the end of follow-up, all patients in group A survived, while in group B three patients (6.1%) receiving lamivudine, and four (7.8%, P>0.05) receiving combinational therapy died; more than 90% of all survivals had their HBV DNA loss. The HBeAg/anti-HBe seroconversion rate in patients of group A treated with interferon alpha (9/17, 52.9%) was higher than that in patients treated with combinational lamivudine and matrine (5/16, 31.3%, P<0.05), which was higher than that in the patients treated with lamivudine alone (1/17, 5.9%, P<0.01), and the Knodell histological activity index score in patients treated with lamivudine (7.2+/-0.8, P<0.05) was lower than that in patients treated with interferon alpha (8.2+/-1.3, P<0.05), and the best efficacy was found in receiving combinational therapy (6.9+/-0.7, P<0.01); Lamivudine or lamivudine in combination with matrine significantly inhibited the intrahepatic inflammatory activities, but had no effect on the existing fibrosis in group B patients. CONCLUSION Long term nucleotide analogues treatment may delay the progress of fibrosis in hepatitis B-induced hepatic failure survivals, and the administration of matrine in time may further enhance the anti-fibrotic effect of nucleotide analogues.