We aimed to identify predictor of HBsAg seroconversion using serum quantitative pg-RNA, HBcrAg and HBsAg in CHB patients with anti-viral therapy.A total of 335 patients with anti-viral therapy between 2013 and 2017 were enrolled, only 23 achieved the seroconversion of HBsAg, other 138 patients without seroconversion of HBsAg were selected randomly in 312 patients. The samples date of 161 patients were analyzed at different time. We defined the decrease titer of pg-RNA, HBcrAg and HBsAg from baseline to 6 months and baseline to 12 months as Δpg-RNA, ΔHBcrAg and ΔHBsAg, then we used the Δpg-RNA, ΔHBcrAg and ΔHBsAg to predict HBsAg seroconversion.About 6.9% of patients achieved HBsAg seroconversion after a median of 3.61 years' treatment. Using ROC to predict seroconversion of HBsAg, ΔHBsAg of 0.64 log10 IU/mL with AUC of 0.886 (0.802, 0.969; 95% CI) at 6 months and ΔHBsAg of 1.45 log10 IU/mL with AUC of 0.939 (0.868, 1.000; 95% CI) at 12 months had the maximized Youden's index. The comparison of HBcrAg "conversion" rates using Kaplan-Meier method between 23 patients with HBsAg conversion and 138 patients with HBsAg no conversion indicated that the two groups had significant difference at the time of antiviral discontinuation (p = 0.0124).According to our results, we can use ΔHBsAg to pick out the appropriate patients who have the potential to achieve seroconversion by sticking to antiviral therapy, that is very important to reach the target of functional cure or even clinical cure.