Ovarian cancer is the fifth leading cause of cancer-related death in women in the United States. Because the success of early screening is limited and most patients with advanced disease develop resistance to multiple treatment modalities, the prognosis is poor. Despite the continuous development of surgery and chemotherapy has revolutionized cancer cure, recurrence remains a major problem occurring in patients with advanced cancer after treatment. Thus, it is essential to improve our understanding of the pathogenesis of ovarian cancer to develop more effective treatments. In this review, we discuss the underlying molecular mechanisms leading to chemotherapy resistance. We summarize the benefits and potential challenges of nanocarrier-delivered small interfering RNA (siRNA) in clinical applications and analyze its feasibility in the treatment of chemotherapy-resistant ovarian cancer. We aim to promote collaborative studies of nanocarrier-delivered siRNAs for therapeutic purposes and improve long-time survival rate and the quality of life of patients with ovarian cancer.