Copper, an essential transient element, can be toxic to cells when present in excess. Altered copper homeostasis is involved in pathological events of many diseases. Human CUTA isoform2 is a member of cation tolerance protein (CutA1) family. In this study, we examined the effect of CUTA isoform2 overexpression on copper toxicity. It was shown that overexpressed CUTA isoform2 sensitized HeLa cells to copper toxicity by promoting copper-induced apoptosis. The inhibition effect of excessive copper on cell proliferation was also enhanced by overexpressed CUTA isoform2. So CUTA isoform2 was implicated to be involved in the cytotoxicity of copper.