Ovarian cancer is the most lethal gynecological tumor. Although surgery and chemotherapy can alleviate the disease, the prognosis for ovarian cancer remains poor. Compounds derived from natural products have been shown to be effective against a variety of diseases, including cancer. 6-Shogaol, active substances isolated from ginger, has been reported to induce apoptosis in ovarian cancer cells, but the mechanism remains unclear. In this study, we demonstrated that 6-shogaol had a direct cytotoxic effect on ovarian cancer cells by inducing ER stress to inhibit the expression of NF-κB (P-P65), thereby upregulating FOXO3a/Bim axis to induce apoptosis. These results reveal the relationship of ER Stress, NF-κB (p-p65) and FOXO3a/Bim axis in ovarian cancer cells. Our study provides new insights into the use of 6-Shogaol in the treatment of ovarian cancer.