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Objective: The present study evaluated the effect of parthenolide on growth and apoptosisregulatory genes of human cervical cancer (SiHa) and breast cancer (MCF-7) cell lines. Materials and methods:The cytotoxic activity of parthenolide (3.5-21 mM) was examined by MTT and LDH assays at 24 and 48 h time intervals. Apoptotic activity was evaluated by expression analysis of multiple apoptosis-regulatory genes (i.e., p53, Bcl-2, Bax, caspase-3, -6, and -9) by reverse transcriptase-PCR and DNA fragmentation assay. Results: Parthenolide inhibited the growth of SiHa and MCF-7 cell lines in a concentrationdependent manner at 24 and 48 h time intervals (p50.001). The IC 50 value of parthenolide against SiHa and MCF-7 cells were 8.42 ± 0.76 and 9.54 ± 0.82 lM, respectively. Parthenolidetreated cells showed up-regulation of p53, Bax, caspase-3, -6, and -3 genes and down-regulation of Bcl-2 gene (p 0.008). At IC 50 , the p53 gene was up-regulated by 9.67-and 3.15-fold in SiHa and MCF-7 cells, respectively. The Bax to Bcl-2 ratio was 3.4 and 2.3 for SiHa and MCF-7 cells, respectively. Also, the fragmented genomic DNA in parthenolide-treated cells showed the signs of apoptosis. Conclusion: Our study endorsed the biological activity of parthenolide and demonstrated the parthenolide-induced growth inhibition and apoptosis in SiHa and MCF-7 cells by modulating the expression of apoptosis-regulatory genes.