Objective: To observe the impact of exogenous growth hormone (GH) on the axis of GH/insulin-like growth factor I (IGF-I)/insulin-like growth factor binding protein (GFBP) in colon cancer-bearing nude mice. Methods: Nude mice xenograft models of human colon cancer were established by using human colon cancer HCT116 cells. Subsequently, 48 tumor-bearing mice were equally randomized into normal saline treatment group (NS group), fluorouracil treatment group (FU group), GH treatment group (GH group) and FU plus GH treatment group (FU+GH group), and all treatment regimens were continued for 6 days. Mice were sacrificed to collect the blood and tumor xenograft samples at 24 and 72 h after the termination of regimens with 6 mice in each group. The serum contents of GH, IGF-I and IGFBP-3 were determined by ELISA assay, and the mRNA expressions of IGF-I, IGF-I receptor (IGF-IR) and IGFBP-3 in xenograft were detect by RT-PCR method. Results: The results of ELISA showed that the serum levels of GH, IGF-I and IGFBP-3 were significantly increased in GH group and FU+GH group compared with either NS group or FU group at 24 h after regimen discontinuation (all P<0.05); at 72 h after regimen discontinuation, the serum levels of GH and IGF-I were similar among groups (both P>0.05), but the IGFBP-3 levels in GH group and FU+GH group were still higher than that in NS group or FU group (all P<0.05). The results of RT-PCR showed that the mRNA expressions of IGF-I and IGF-IR were obviously decreased but IGFBP-3 mRNA expression was markedly increased in tumor xenografts in either GH group or FU group or FU+GH group compared with NS group at 24 h after regimen discontinuation; at 72 h after regimen discontinuation, both IGF-I and IGF-IR mRNA expressions were similar among groups, but IGFBP-3 mRNA expressions in above three groups were still higher than that in NS group. Conclusion: The alteration in GH/IGF/IGFBP axis resulting from short-term exogenous GH application exerts no growth-promoting effect on tumor xenograft of human colon cancer.