Ovarian cancer is the most lethal neoplasm of the female genital tract. Despite progress with chemotherapy, surgery and supportive care, the death rate remains extremely high. Gene silencing therapy represents a possible opportunity to advance the management of ovarian cancer patients. The concept of gene silencing therapy, which is based on RNA interference (RNAi) phenomenon, requires selection of targeted genes and development of a strategy for genetic drug development. Recently, plenty of research studies in ovarian cancer genetics have been published. Although they can be analyzed regarding candidate gene selection, the therapeutic effect of particular gene silencing can only be evaluated experimentally at this time. Obviously, the correct choice and application of a genetic drug delivery system determines the efficacy of gene silencing. Complexation of therapeutic nucleic acids with cationic polymers, cationic lipids, or their combination, represents a main strategy of non-virus-mediated delivery of genetic drug. Owing to a tendency of ovarian cancer to spread through the abdominal cavity, a delivery system should allow intraperitoneal mode of administration. Therefore, clinical application of RNAi may rely on a combination of biosciences and nanotechnology: in particular, identifying optimal small interfering RNAs (siRNAs) against optimal target genes and developing an efficient system for siRNA delivery into the cancer cells.