Despite the development of effective HPV screening and vaccination programs in women, cervical c ancer ranks first in cancer-related deaths. In order to prevent the side effects of chemotherapeutic agents, studies on the use of natural compounds in the treatment of cervical cancer are becoming increasingly common. Esculetin, a coumarin derivative from natural compounds, is a pharmacological substance with anti-inflammatory, antioxidant, anti-tumor, neuroprotective effects. In various studies, esculetin has been found to induce apoptosis in colon cancer, breast cancer, and cervical cancer via JNK, ERK, ROS mediated mitochondrial pathway or ER stress activation pathways. HeLa cells and HEK cells were cultured. MTT analysis was performed to determine the IC50 dose of the esculetin. Expression levels of apoptotic genes (BAX, BAK, BAD, APAF-1 and p53) and antiapoptotic genes (BCL-2, BCL-XL) were detected by qPCR. The IC50 dose at which esculetin inhibited the viability of HeLa cells was determined as 800 μM. In addition, esculetin down-regulated antiapoptotic genes BCL-2 and BCL-XL, while up-regulated apoptotic genes such as BAK, APAF-1, p53, BAD, BAX. Current findings showed that esculetin has apoptotic effects on HeLa cells.