Objective To investigate the efficacy and safety of Entecavir in the treatment of chronic hepatitis B.Method Seventy-two patients with chronic hepatitis B were assigned to Entecovir (experimental) group (n=30) and LAM (control) group (n=42) randomly.Each patient in the experimental group received 0.5mg every day.Each patient in the control group received 100mg every day.All the patients were treated for 48 weeks.After 24 and 48-weeks of treatment, serum HBV DNA levels were measured and liver function tests.The HBV serology and safety assessments were also conducted.Results The mean reduction of HBV DNA from baseline at 24 and 48 weeks was significantly in the Entecovir group compared with that in the LAM group (-5.48, -6.87log10copier/ml and-2.84, -5.34log10 copies/ml, P<0.001) .In the Entecavir group, the ratio of virological response and ALT normalization at 24 and 48-weeks were higher than those in the LAM group.There was no significant difference between the two groups in the portion of HBeAg reduction, HBsAg seroconversion and incidence of adverse events.There was no severe advere event in this trial.Conclusion Entecavir is effective and safe for the treatment of chronic hepatitis B patients.