During interferon (IFN) treatment in chronic hepatitis B (CHB) patients, HBsAg often declines to a plateau. This study aimed to investigate HBsAg loss rate in patients receiving extended IFN treatment after the plateau and in patients who suspended IFN treatment for 3-6 months and received IFN treatment again after the interval. In this retrospective study, 403 CHB patients with a plateau of HBsAg decline after 24 weeks pegylated IFN α (PEG-IFN α) treatment were collected. After the plateau, patients chose PEG-IFN continuous treatment or re-treatment after an interval. HBsAg loss rate in intermittent treatment group was significant higher than that in continuous treatment group ( p=0.001), which were 21.58% and 8.63% ( p=0.002) in 278 cases PSM matched population. Multivariate COX regression showed that intermittent therapy ( p=0.017) and the HBsAg level of second time point of plateau ( p<0.001) were independent factors for HBsAg loss. Multivariate COX regression of PSM matched population showed baseline HBsAg level ( p=0.043), HBsAg level at the second time point of plateau ( p=0.000), and intermittent therapy ( p=0.004) were independent factors for HBsAg loss. In CHB patients receiving PEG-IFN based treatment, compared to continuous treatment, intermittent treatment was more beneficial for achieving HBsAg loss once HBsAg decline reaches a plateau.