Cadmium (Cd) is an environmental toxic heavy metal that causes renal dysfunction. Cd triggers renal dysfunction through proximal tubular cell toxicity. Our previous study demonstrated that Cd changed the activities of various transcription factors in human proximal tubular HK-2 cells. Interestingly, several GATA family members were included in the transcription factors whose activities were decreased by Cd treatment. The GATA family has diverse roles in cell proliferation, tissue development, disease regulation, and carcinogenesis. In this study, we examined whether knockdown of GATA family members affected the viability of HK-2 cells. The single knockdown of GATA1, GATA3 or GATA6 using siRNA significantly decreased HK-2 cell viability. In particular, GATA6 knockdown led to the greatest effect on HK-2 cells viability. Cd increased mRNA levels of GATA3 and GATA6 but did not affect that of GATA1. The GATA family may regulate the expression of downstream factors involved in common pathway. Therefore, the effect of combined knockdown of GATA1/3/6 on the viability of HK-2 cells was examined. Our results indicated that the effect on HK-2 cell viability following knockdown of multiple GATA family members was comparable to the single knockdown of GATA6. These results suggest, therefore, that multiple GATA family members may be involved in modulating Cd renal toxicity through a common pathway.