Background: Breast cancer metastasis suppressor 1 (BRMS1) is a potent metastasis suppressor of various types of malignancies, including melanoma and ovarian cancer. Unfortunately, the clinical data regarding its role as a true metastatic suppressor and its efficacy as a prognostic marker and therapeutic target remain controversial. This study was designed to investigate the effect of BRMS1 on the invasion and metastasis of human ovarian cancer cells and its potential underlying mechanisms. Materials and Methods: BRMS1 small interfering RNAs (siRNAs) or control siRNAs were transfected into the OVCAR3 human ovarian cancer cell line. Invasion and migration activities were assessed using the Transwell invasion and migration assay. Protein levels of nuclear factor-κB (NF-κB) subunit p65, osteopontin (OPN) and urokinase-type plasminogen activator (uPA) were evaluated by Western blot, immunofluorescence and immunocytochemistry methods. Results: Successful knockdown of BRMS1 was verified by quantitative real-time RT-PCR and Western blot. The invasion and migration capacities of OVCAR3 cells were significantly enhanced in the BRMS1-silenced group, compared to controls (p < 0.05). Silencing of BRMS1 significantly induced the expression of NF-κB subunit, p65, uPA, and OPN proteins. Conclusions: BRMS1 inhibits expression of p65, uPA and OPN protein. In turn, this leads to inhibition of ovarian cancer cell invasion and metastasis. This study unveils a potential novel mechanism by which BRMS1 inhibits metastasis of ovarian cancer cells.