Objective：The study aimed to investigate the impact of polyethylene glycol-conjugated recombinant human growth hormone（PEG-rhGH）treatment on immune function in children with growth hormone deficiency（GHD），by analyzing changes in lymphocyte subsets，immunoglobulin levels，and T helper cell（Th1/Th2）cytokines before and after treatment. Methods：Fifty-five children diagnosed with GHD were enrolled as study participants from May 2022 to June 2023 at the Department of Pediatrics of Huai’ an First People’s Hospital and Hongze District People’s Hospital. According to the preferences of the participants，they were allocated into a control group（n=25）and a PEG-rhGH group（n=30）. The control group received guidance on exercise，diet，and sleep，while the PEG-rhGH group received PEG-rhGH treatment in addition to these interventions. Measurements of height，bone age，BMI，insulin-like growth factor -1（IGF -1），lymphocyte subsets，Th1/Th2 cytokines，and immunoglobulin（Ig）levels were conducted at baseline and 3 months post-treatment. The changes in various parameters before and after the intervention were compared. Results：Before treatment，there were no significant differences in the baseline levels of the various indicators between the two groups. After 3 months of treatment，the standard deviation of height，growth rate，and serum IGF-1 level in the PEG-rhGH group significantly increased compared to pre-treatment levels and were notably higher than those in the control group. After treatment，the PEG-rhGH group demonstrated a significantly higher proportion of CD3⁺ ，CD4⁺ and CD4⁺ /CD8⁺ as well as elevated levels of IgA，IgM，and IgG compared to the control group，while the proportion of CD8⁺ cells was notably lower in the PEG-rhGH group than in the control group，There were no significant differences in the proportion of CD19 ⁺ and CD3^- CD16 ⁺ CD56 ⁺ cells between the two groups. Additionally，the levels of Th1/Th2 cytokines，interleukin（IL）-2，IL-6，and tumor necrosis factor-α（TNF-α）in the PEG-rhGH group were significantly lower after treatment compared to before，and were significantly lower than those in the control group. There were still no significant differences in the levels of IL-4 and interferon-γ（IFN-γ）between the two groups. Conclusion：PEG-rhGH treatment not only improves the height of GHD children but also affects their cellular immunity and humoral immunity.