Study Objectives: Saffron and its main components have been shown to have anti-tumor and anti-cancer effects in animal studies and human cancer cell cultures. This study aimed to investigate the anti-cancer effects of saffron on human ovarian cancer cells. Methods: Powder of saffron was applied to the HO–8910 cell lines. Cell viability was determined. ELISA test is used to examine the activity of caspase-3 and expression of AIF, gadd153, grp78, caspase 3, bax, bcl-2, wee 1, which are apoptotic pathway’s mediators. Active ERK (p-ERK), active JNK (p-JNK) active AKT (p-AKT), and active mTOR (p-mTOR) were also analyzed by ELISA. Results: Saffron treatment reduced the viability of ovarian cancer cells. Saffron treatment increased activity of caspase 3 and expression of bax, wee 1, gadd153, grp78, and AIF and decreased bcl-2 which is anti-apoptotic protein. Saffron also decreased the activity of p-ERK, p-JNK, p-AKT, and p-mTOR in ovarian cancer cells. Conclusion: This study revealed that saffron has a beneficial effect on cancer treatment. Saffron may show a synergistic effect with various chemotherapeutics while directing the cancer cell to death. Crocetin, one of its active components, has shown a synergistic anti-cancer effect combined with cisplatin. Saffron induced apoptosis via ER stress, AKT/mTOR, and MAPK pathways in the ovarian cancer cell line.Keywords: Saffron, ovarian cancer, apoptosis, MAPK, AKT/mTORIntroductionAlthough great improvement in the medical and pharmaceutical field, cancer has remained as an incur-able disease. This led the researchers to seek alternative treatments. Traditional medicine knowledge has been revised all over the world and therapeutic effects began to be studied in depth. Crocus Sativus is the raw mate-rial of saffron, the most expensive spice in the world, and has been used in traditional medicine for centuries.Saffron has been used in traditional medicine as an appetizer, stomach acid regulator, tranquilizer, expectorant, aphrodisiac, abortifacient, for treatment of liver diseases, gas, and spasm relief, tooth and gum ailments, insomnia, cough, bronchitis, colds, fever, heart diseases, and cancer (1-3). Modern biomedical findings showed that saffron and its components may be useful in the treatment of neuro-degenerative dis-eases and resultant memory problems, ischemic neu-ropathy, age-related macular degeneration, coronary artery disease, blood pressure abnormalities, acute and chronic inflammatory diseases, mild-moderate depres-sion, seizure, and Parkinson’s disease (4,5). In addition, anti-oxidant, anti-mutagenic, anti-genotoxic and tu-moricidal effects have been found saffron to have (6,7).As a result of the chemical analysis of saffron flow-ers (Figure 1), it has been determined that it has more than 150 components. It is known that the strongest