Objective To observe the incidence of spontaneous clearance of hepatitis B virus (HBV) DNA in chronic hepatitis B (CHB) patients ,and to investigate the related factors of the spontaneous clearance of HBV DNA and to determine the time to start antiviral therapy .Methods Patients who met the inclusion criteria were recruited from the follow-up cohort of chronic HBV infection from January 2008 to August 2017 for observation .The liver function including alanine aminotransferase (ALT) levels ,HBV DNA load and serum markers of HBV were measured at baseline ,month 1 ,month 3 and month 6 of follow-up . Evaluation index included cumulative HBV DNA negative conversion rate and cumulative HBeAg negative conversion rate .Multivariable analysis was used to analyze the factors associated with the spontaneous clearance of HBV DNA .Results A total of 116 patients were recruited in this study .All the patients showed ALT level elevation at baseline .Without antiviral treatment ,the cumulative HBV DNA negative conversion rate was 12 .9％ after 6-month observation .HBeAg negative conversion rate was 22 .5％ .Multivariable analysis showed that patients without a family history of HBV infection ,baseline ALT level >3 times the upper limit of normal (ULN) and HBV DNA level <6 lg copies/mL had higher cumulative HBV DNA spontaneous clearance rate .HBV DNA negative conversion rate in patients whomet all the above three conditions was up to 75％ .Conclusions In CHB patients and ALT level elevation for the first time , some patients could achieve spontaneous clearance of HBV DNA without antiviral therapy .Patients without a family history of HBV infection ,baseline ALT level >3 ULN and HBV DNA level <6 lg copies/mL have higher rate of cumulative HBV DNA spontaneous clearance .