Objective To observe the treatment efficacy of polyethylene glycol recombinant growth hormone on idiopathic short stature children and its effect on the expression of p53 and p21waf/cip1. Methods A total of 121 children with idiopathic short stature treated in Ya′an Maternal and Child Health Care Planning Service Center from February 2015 to October 2016 were selected in this study and divided into control group (n=61) and treatment group (n=60) according to random number table method.The control group was treated with nutrition therapy, while the treatment group was treated with polyethylene glycol recombinant growth hormone in addition to nutritional therapy.The clinical efficacy and the adverse reactions incidence were observed, and the differences on IGF-1/IGFBP-3 as well as the expression of p53 and p21waf/cip1 before treatment, 3 months, 6 months after treatment were compared. Results The height of the treatment group was significantly higher than that of the control group after the treatment (P<0.05).The levels of IGF-1 and IGFBP-3 were increased with treatment time prolonged.The levels of IGF-1 and IGFBP-3 in the treatment group were significantly higher than those of the control group at the same point (P<0.05).There was no significant difference on the serum p53 mRNA levels between treatment group and control after treatment (P>0.05), while the expression level of p21waf/cip1 mRNA in the treatment group decreased with treatment time prolonged and it was significantly lower than that in the control group (P<0.05). Conclusions Polyethylene glycol recombinant human growth hormone has a significant therapeutic effect on idiopathic short stature children.And it is of great value in clinical application because of its efficacy in increasing the height of patients and improves cell proliferation.