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 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 Huaian First People's Hospital and Hongze District People's Hospital. According to the preferences of the participants, they were allocated into PEG-rhGH group (n=30) and control group (n=25). The control group received exercise, diet, and sleep interventions, while the PEG-rhGH group was adtered PEG-rhGH treatment based on these interventions. Measurements of height, bone age, BMI, insulin-minislike growth factor-1 (IGF-1), lymphocyte subsets, helper T cell cytokines, and immunoglobulin levels were conducted at baseline and 3 months post-treatment. Comparative analysis was performed to assess changes in various parameters before and after the intervention. Results: There were no significant differences between the two groups prior to treatment. After 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 was no significant disparity in the proportion of CD19+ and CD3-CD16+CD56+ cells between the two groups. After treatment, IL-2, IL-6, IL-10 and TNF-α cytokine levels significantly decreased in the PEG-rhGH group while IL-4 and IFN-γ levels remained unchanged compared to those in control group. Conclusion: When PEG-rhGH enhances stature among children with GHD ，it ?also influences the level of cellular and humoral immune.