Punicalagin, a naturally occurring compound found in pomegranate, has gained attention for its potential anticancer properties. This study investigated the impact of punicalagin on the expression levels of key apoptosis-related genes, specifically BAD, BCL2, BCL-xl, and Bax, in hepatocellular carcinoma (HCC) cells. The HepG2 cell line was subjected to varying concentrations of punicalagin (100 and 150 μg), and subsequent analysis focused on the expression levels of the target genes. The results revealed a significant decrease in mRNA expression levels of BAD, BCL2, and BCL-xl in punicalagin-treated HepG2 cells compared to untreated cells. Notably, the reduction in expression levels was more pronounced with the higher concentration of 150 μg. Interestingly, the treatment with punicalagin led to an upregulation of Bax in liver cancer cells.To explore the potential interaction between punicalagin and the apoptosis-regulating targets, molecular docking analysis was employed. The analysis substantiated a strong binding affinity between punicalagin and BAD, BCL2, BCL-xl, implying a direct interaction between the compound and these targets.Collectively, this study sheds light on the inhibitory effect of punicalagin on apoptosis-mediated targets in HCC cells. The findings propose that punicalagin might exert a regulatory influence on apoptosis in liver cancer cells. Further investigation is required to validate these findings and to elucidate the therapeutic potential of punicalagin in hepatocellular carcinoma tumorigenesis.