Abstract Background and Aims Interleukin‐2 (IL‐2) can be used as an adjuvant therapy when pegylated interferon alpha (Peg‐IFN‐α) does not effectively promote hepatitis B surface antigen (HBsAg) loss, but the relevant timing, kinetic patterns, and prognostic associations of this intervention are unclear. Methods A total of 115 patients with chronic hepatitis B (CHB) treated at our institution between October 2018 and March 2021 were included in this retrospective analysis. They were divided into two kinetic patterns by using K‐medoids cluster analysis. Profile and prognostic associations were statistically analyzed between the two patterns. Results After baseline standardization, before the intervention, the relative HBsAg level showed a continuously increasing trend, but after the intervention, it showed a continuously decreasing trend. Based on the relative change in the HBsAg level, two kinetic patterns, namely, a fluctuation platform pattern and a stepwise growth pattern, were identified by using K‐medoids cluster analysis for all 115 patients before IL‐2 intervention. Profile analysis showed that there were statistically significant differences between the two patterns before IL‐2 intervention (p