Objective To investigate the correlation between the expression level of HBV pgRNA and the responsiveness to nucleoside analogs（NAs）in patients with chronic hepatitis B（CHB）. Methods A total of 237 CHB patients diagnosed in the outpatient department of our hospital from January 2020 to June 2021 were selected as the research subjects. All patients met the NAs treatment standard. Before treatment，all patients were tested for HBV pgRNA，and the general data，laboratory data and imaging data were collected. NAs ⁃ related drugs were administered for a 24⁃week treatment plan. The treatment response of the patients during the treatment was counted and grouped at the end of the treatment. logistic regression was used to analyze the correlation between treatment response and HBV pgRNA，and ROC curve was drawn to analyze the predictive value of HBV pgRNA for treat⁃ ment response. Results As of December 2021，the treatment period of all patients had expired，and a total of 207 patients had completed the treatment and follow⁃up plan prescribed in this study，with a completion rate of 87.34%. Patients were divided into complete response group（n = 87），partial response group（n = 79），and poor response group（n = 41）. There was no statistically significant difference in general data among the three groups（P > 0.05）. There were significant differences in HBV ⁃ DNA，HBV pgRNA，HBsAg，HBeAg and HBeAb among the three groups（P < 0.05）. The HBV⁃DNA，HBV pgRNA，HBsAg，and HBeAg in the poor response group were higher than those in the other two groups，but HBeAb was lower，and the difference was statistically significant（P < 0.05）. The HBV pgRNA in the partial response group was higher than that in the complete response group，and the differ⁃ ence was statistically significant（P < 0.05）. There was no significant difference in HBV ⁃DNA，HBsAg，HBeAg and HBeAb between the partial response group and the complete response group（P > 0.05）. HBV ⁃DNA，HBVpgRNA，HBsAg and HBeAg were independent risk factors for treatment response，while HBeAb was an indepen⁃ dent protective factor for treatment response（P < 0.05）. The AUC of HBV pgRNA in response to NAs treatment was significantly bigger than that of HBV ⁃DNA，HBsAg，HBeAg，and HBeAb（P < 0.05）. Conclusion HBV pgRNA is significantly correlated with the response to NAs treatment in CHB patients.