Abstract: Objective To analyze the short-term effectiveness and safety of recombinant human growth hormone (rhGH), gonadotropin-releasing hormone analogue (GnRHa) or their combination in the treatment of early puberty children with idiopathic short stature (ISS). Methods A total of 60 early puberty children with ISS who were admitted to the Affiliated Hospital of Xuzhou Medical University from September 2017 to June 2019 were enrolled. According to their treatment strategies, they were divided into three groups (n=20): a rhGH treatment group, a GnRHa treatment group, and a combined treatment group. They were regularly monitored for their height, high predict lifetime (PAH); fasting glucose, thyroid function, liver function; serum insulin-like growth factor 1 (IGF-1). Results After 1 year of follow-up, children in the three groups produced statistical differences in height, bone age and PAH, compared with those before treatment (P<0.05). The combined treatment group produced remarkably higher growth rate and PAH than the rhGH treatment group and the GnRHa treatment group (P<0.05). There was no significant difference in blood glucose, thyroid function and liver function among the three groups (P>0.05). Conclusions The combined use of rhGH and GnRHa showed good effectiveness in increase growth rate and PAH improvement, which is superior to treatment with rhGH or GnRHa alone, without obvious adverse reactions.