【Objective】To screen the factors that may affect HBsAg spontaneous seroclearance and to explore the real-life situation of HBsAg spontaneous seroclearance in a large cohort of chronic hepatitis B infection patients with longterm follow-up.【Method】All the patients came from the SCHEMA cohort（South China Hepatitis Monitoring and Admin? istration cohort）with chronic HBV infection who were followed up in the out-patient department of the third affiliated hospital，Sun Yat-sen University from Jan. 2006. The data were regularly collected at 3 or 6 months interval，including demographic characteristics，baseline，dynamic changes of the biochemical，virological，serological and imagery indicators during the follow-up period，and then univariate and multivariate COX regression model were taken to screen the influ? ence factors.【Result】54 patients obtained HBsAg spontaneous seroclearance in 974 chronic hepatitis B infection patients after up to 10 years follow-up. We found that age（especially≥50，HR=2.647，P=0.001），BMI（especially≥28，which means very fat，HR=3.401，P=0.004），baseline HBV DNA level（especially<104 U/mL，HR=11.798，P=0.001），portal length（HR=1.017，P=0.013），right liver oblique diameter（HR=1.026，P=0.007）and baseline HBsAg titer（especially> 2000 U/mL，HR=0.056，P<0.001）can significantly affect HBsAg seroclearance by univariate COX regression analysis. In the multivariate COX regression analysis，baseline HBsAg titer（HR=0.071，P<0.001）and baseline HBV DNA quanti? tation（HR = 0.819，P = 0.005）had an independent effects on HBsAg spontaneous seroclearance.【Conclusion】For the chronic hepatitis B infection patients without antiviral treatment，Baseline HBV DNA levels and baseline HBsAg levels were independent factors of HBsAg spontaneous seroconversion. Moreover，the patients with baseline HBV DNA lower levels（<104 U/mL）and HBsAg lower levels（<2 000 U/mL）were more likely to obtain HBsAg spontaneous seroclearance.