Objective To investigate the effects of a disintegrin and metalloprotease domain 8 (ADAM8) gene on the proliferation of colon cancer cells HCT8, and the phosphatidylinositol-3-kinase/protein kinase B/the mammalian target of Rapamycin (PI3K/Akt/mTOR) signal transduction pathway. Methods The HCT8 cells were cultured in vitro, and transfected with ADAM8 overexpression plasmid vector (overexpression group) and ADAM8 gene RNA interference plasmid vector (interference group) respectively, A control group was set up. Cell proliferation was detected by 5-Ethynyl -2’-deoxyuridine (EdU) and 3-(4, 5-Dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) methods. The PI3K enzyme activity was detected by PI3K activity assay kit. The relative expression of Akt, phosphorylated Akt (p-Akt) and the expression of mTOR were detected by Western blotting. Results (1) The expression of ADAM8 in overexpression group was significantly higher than that in control group (t=1.143, P=0.035), while the expression of ADAM8 in interference group was significantly lower than that in control group (t=1.203, P=0.027), which indicated that overexpression vector and interference expression vector were successfully constructed. (2) The cell proliferation capacity of overexpression group [(1.31±0.15) copies/ml] was significantly higher than that of control group [(1.00±0.10) copies/ml, t=1.157, P=0.033], and the cell proliferation ability [(0.71±0.09) copies/ml] in overexpression group was significantly lower than that of control group [(1.00±0.10) copies/ml, t=1.172, P=0.031]. (3) As compared with the control group, there was no significant difference in the changes of enzyme activities of PI3K in the overexpression and interference groups. The expression of p-Akt was increased, and the expression of p-Akt was decreased after the overexpression of ADAM8. The difference was statistically significant (t=1.319, P=0.018). The expression of mTOR was increased, and the expression of mTOR was decreased after the overexpression of ADAM8. The difference was statistically significant (t=1.390, P=0.014). Conclusion ADAM8 can enhance the expression of Akt and the phosphorylation of mTOR, stimulating the proliferation of HCT8 cells. Key words: Solution of integrin like metalloproteinase 8; Colon cancer; Interference expression