Objective To investigate the value of serum hepatitis B virus(HBV)RNA for predicting hepatitis B virus e antigen(HBeAg)clearance and seroconversion after nucleoside(acid)analogs(NAs)treatment in patients with chronic hepatitis B(CHB).Methods Serum samples were collected from 178 CHB patients who received NAs monotherapy in Weihai Hospital affiliated to Shandong University of Traditional Chinese Medicine from February 12,2017 to February 21,2019.Serum HBV RNA levels were analyzed by real-time fluorescence-based quantitative PCR at baseline and after NAs treatment.Results The patients with HBeAg clearance and seroconversion showed significantly lower serum HBV RNA levels at baseline,6 months and 12 months of treatment compared with those without HBeAg clearance and seroconversion(P＜0.001).During follow-up,the patients with lower baseline HBV RNA levels had higher rate of cumulative HBeAg clearance(Log Rank x2=11.282,P=0.001)or seroconversion(Log Rank x2=10.739,P=0.001)than the patients with higher baseline HBV RNA levels.Cox regression model analysis indicated that serum HBV RNA levels at baseline,6 months and 12 months of treatment were an independent predictor for HBeAg clearance and seroconversion in CHB patients(P＜0.05).The area under the ROC curve(AUC)of baseline serum HBV RNA level was 0.808(95％CI:0.743-0.872)for predicting HBeAg clearance and 0.824(95％CI:0.763-0.885)for predicting seroconversion.The AUC of HBV RNA level at 6 months of treatment was 0.830(95％CI:0.765-0.894)for predicting HBeAg clearance and 0.732(95％CI:0.657-0.808)for predicting seroconversion.The AUC of HBV RNA level at 12 months of treatment was 0.737(95％CI:0.641-0.833)for predicting HBeAg clearance and 0.757(95％CI:0.671-0.842)for predicting seroconversion.The AUC of baseline HBV RNA level combined with HBV RNA decline at 6 months of treatment was 0.856(95％CI:0.795-0.917)for predicting HBeAg clearance and 0.864(95％CI:0.802-0.926)for predicting seroconversion.The AUC of baseline HBV RNA level combined with HBV RNA decline at 12 months of treatment was 0.881(95％CI:0.826-0.936)for predicting HBeAg clearance and 0.848(95％CI:0.784-0.911)for predicting seroconversion.Conclusions Serum HBV RNA levels have high predictive value for HBeAg clearance and seroconversion after NAs therapy in CHB patients,suggesting that HBV RNA levels are helpful for identifying non-responders and informing combination therapy.