Objective To explore the effects of shRNA-mediated downregulating lncRNA HOTAIR on the invasion, nude mouse tumorigenicity and snail expression of epithelial ovarian cancer SKOV3 cells. Methods The expression of lncRNA HOTAIR was detected by RT-PCR in SKOV3 cells. The shRNA targeting the lncRNA HOTAIR gene was cloned into RNA interference plasmid. The construction shHOTAIR vector was transfected into ovarian cancer SKOV3 cells by lipofectamine 2000, and the stably transfected cells were isolated by G418 and single clone selection. The downregulating expression of lncRNA HOTAIR was detected by quantitative real time PCR(qRT-PCR). The characteristics of shHOTAIR transfected SKOV3 cells were analyzed from the assays of invasion and nude mouse tumorigenicity, as well as the expression of snail and E-cadherin mRNA detected by qRT-PCR, and snail detected by immunohistochemistry and Western blot methods in xenograft tumor, respectively. Results The lncRNA HOTAIR expression was proved by RT-PCR in SKOV3 cells. The lncRNA HOTAIR expression in shHOTAIR transfected SKOV3 cells was significantly lower than the scramble control (PshHOTAIR transfected SKOV3 cells show that the invasion ability was significantly decreased compared with the scramble control (PPshHOTAIR-SKOV3 xenograft tumor was significantly decreased compared with the control scramble- SKOV3 group (PHOTAIR low expression resulted in increasing E-cadherin and decreasing snail expression detected by qRT-PCR in the shHOTAIR transfected SKOV3 cells of xenograft tumor, compared with the scramble control (PHOTAIR expression in SKOV3 cells with RNA interference can decrease snail, increase E-cadherin and significantly reduce the invasion and tumorigenicity of epithelial ovarian cancer SKOV3 cells. These results suggest that the lncRNA HOTAIR could be an effective therapeutic target for human epithelial ovarian caner treatment.