Zinc-finger protein 217 (ZNF217), a candidate oncogene on 20q13.2, can lead cultured human ovarian and mammary epithelial cells to immortalization, which indicates selective expression of ZNF217 affecting 20q13 amplification during critical early stages of cancer progression. In this study, we tested the hypothesis that ZNF217 is a key factor in regulating ovarian cancer proliferation and progression. We examined the effect of the inhibition of ZNF217 expression on proliferation and invasion by establishing the ZNF217 knockdown ovarian cancer cell line using RNA interference (RNAi). Our results showed that silencing of ZNF217 resulted in the effective inhibition of ovarian cancer cell growth and invasive ability. The results suggested that ZNF217 might play a crucial role in the proliferation and invasion of ovarian cancer.