High levels of polyamines were observed and were related to a poor prognosis in cancer patients. However, the mechanism is not obvious. The aim of this study is to mimic the extracellular polyamines in a tumor microenviroment and to explore the role of extracellular polyamines in the proliferation and migration of cancer cells. Three different concentrations of polyamines composed of putrescine, spermidine, and spermine were used. Colony formation assay, wound healing assay, and transwell migration assay were performed. Akt1-overexpression cells were constructed. The related protein expression was examined using a western blot. In this study, polyamines promoted colony formation and cell migration in a concentration-dependent and time-dependent manner. Polyamines upregulated the expression of ornithine decarboxylase (ODC), SSAT, Akt1, Akt, hypoxia-inducible factors-1α, vascular endothelial growth factor, and matrix metalloproteinases, and downregulated p27 expression. The effects of combination of polyamines and Akt1 overexpression on colony formation and migration were more obvious than the effects of Akt1 overexpression alone. In Akt1-overexpression cells, polyamines also upregulated the expression of ODC, SSAT, hypoxia-inducible factors-1α, vascular endothelial growth factor, and matrix metalloproteinases and downregulated p27 expression. In conclusion, extracellular polyamines induced proliferation and cancer cell migration by inducing ODC and SSAT expression, and the Akt1-mediated pathway.