Objective: To investigate the effect of silencing ORP-150 gene on the proliferation and metastasis of ovarian cancer cell line SKOV-3 in vitro and to explore its possible mechanism. Methods: The ORP-150 gene of SKOV-3 cells was silenced by lentivirus packaging shRNA method, and then 3 groups were designed: An experimental group (ORP-150 shRNA), a negative control group (NC shRNA) and a blank control group (CON). qPCR and Western Blot were used to detect gene knockout efficiency. CCK-8 method and clone formation assay were used to detect the effect of ORP-150 silencing on cell proliferation ability. Wound Healing and transwell tests were used to detect the invasion and metastasis of ovarian cancer cells. Flow cytometry was used to detect the apoptosis of cells. Western-blot was used to investigate the possible mechanism of ORP-150 gene knockdown on cell phenotype changes. Results: Silencing ORP-150 gene could inhibit the proliferation ability, clone formation ability and transmembrane transfer and diffusion ability of ovarian cancer cells (P<0.05), but had no significant effect on the invasive ability of the cells (P>0.05). The apoptosis of ovarian cancer cells was significantly increased after knockdown of ORP-150 gene (P<0.05). Ovarian cancer cells knocked down ORP-150 gene may affect the cell repair through Wnt signaling pathway and Caspase cascade reaction, and ultimately inhibit cell proliferation and promote apoptosis. Conclusion: Silencing ORP-150 gene inhibits the proliferation and metastasis of ovarian cancer cell line SKOV-3 and promotes cell apoptosis. This effect may be achieved by inhibiting the expression of c-myc, cyclin D1 and caspase-3 proteins through inhibiting the expression of β-catenin in the Wnt signaling pathway and inhibiting the Caspase cascade. ORP-150 gene silencing may be a new target for ovarian cancer treatment.