Cadmium (Cd) is a toxic heavy metal, particularly in the kidney. Zinc transporters have been reported to be responsible for the absorption of Cd in the kidney. Interestingly, we previously found in a DNA microarray that exposure to Cd suppressed the expression of the gene coding for the zinc transporter ZIP1 (SLC39A1) in HK-2 human kidney proximal tubular cells. In this study, we validated by realtime RT-PCR that SLC39A1 gene expression was indeed decreased upon treatment with 40 μM Cd. We also demonstrated that knockdown of SLC39A1 by siRNA transfection conferred resistance to Cd in HK-2 cells. Together, this suggests that gene suppression of SLC39A1 by Cd is involved in the defense mechanism against the Cd toxicity in HK-2 cells.