Background: Recombinant human growth hormone (rhGH) was approved for the therapy of pediatric patients with growth hormone deficiency (GHD) by the Food and Drug Administration (FDA) of the United States in 1985. This study aims to evaluate the effects of rhGH therapy on thyroid function in pediatric patients with GHD. Methods: A total of 55 pediatric patients, who had been diagnosed with GHD and received rhGH therapy for 6-24 months, and who could regularly come to our hospital for outpatient visits from May 1, 2014 to April 30, 2017, were selected for the study. All of the patients were treated for at least six months, among which 44 patients were treated for 12 months, and 32 patients were treated for 18 months, and 16 patients were treated for 24 months. Results: (I) During the course of the rhGH therapy, none of the patients had a free thyroxine (FT4) level lower than the normal lower limit. (II) The FT4 level decreased during the course of the therapy, when compared to the level at baseline, and the difference was statistically significant after 24 months of therapy. In the puberty group, the FT4 level had significantly decreased by the 12th month of therapy, when compared to the baseline, but there was no significant change in the FT4 and thyroid-stimulating hormone (TSH) levels at the remaining observation time points of treatment. Conclusions: Growth hormone (GH) replacement therapy may affect the metabolism of the thyroid hormone in pediatric patients with GHD. During the course of treatment, the changes in thyroid function in pediatric patients with GHD should be regularly monitored in order to identify any abnormal thyroid function in its early stages.