Ovarian carcinoma is one of the most prevalent and lethal gynecological malignancies, and is the fifth leading cause of cancer death among women in the United Stat. Like most malignancies, ovarian cancer is a heterogeneous disease characterized by multiple molecular alterations. These include loss of function of tumor suppressor genes, deregulation of Bcl-2 family proteins, inhibition of caspase activation, and activation of cellular survival signaling pathways, such as HER-2/neu and phosphatidylinositol-3 kinase PI3K/Akt. Over years the use of natural compounds as anticancer agents acquired great importance. Thymoquinone (TQ) is the main bioactive component of the volatile oil of the black seed (Nigella sativa, Ranunclulaceae family). TQ has been used as antioxidant, anti-inflammatory, and antineoplastic medicines for more than 2,000 years. Previous studies reported that TQ exhibited inhibitory effects on cell proliferation of many types of cancer cell lines, including breast adenocarcinoma, lung adenocarcinoma, colorectal cancer, etc. Here, we report that TQ greatly inhibited cell proliferation of cisplatin-resistant ovarian cancer cells (A2780/CP70) 24, 48 and 72 hours after treatment in a concentration-dependent manner. However, our flow cytometry data revealed that TQ is a cell cycle non-specific for CP70 cells. Our results also showed that TQ upregulated PTEN and p53 in CP70 cells while downregulated phospho-Akt in a dose-dependent manner. Current investigations are ongoing to fully understand the mechanism of action of TQ in cisplatin-resistant ovarian cancer cells.