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Background/aim: Lycopene is associated with anticancer effects in various tumor types. However, the exact underlying mechanisms of action of lycopene in human cervical cancer remain to be determined. This study aimed to determine anticancer efficacy and mechanism of lycopene in human cervical carcinoma (HeLa) cells. Materials and methods: HeLa cells were treated with cisplatin (1 µM) alone, lycopene (10 µM) alone, and in combination for 72 h. The cell viability of HeLa cells was assessed via MTS assay. Western blot was used to analyze the expression levels of the nuclear factor-kappa B (NF-kB), B-cell-associated X protein (Bax), nuclear factor erythroid 2-related factor (Nrf2), and B-cell lymphoma 2 (Bcl-2). Results: We found that lycopene acts as a synergistic agent with cisplatin in preventing the growth of HeLa cells. The rates of HeLa cells' viability were 65.6% and 71.1% with lycopene and cisplatin treatment alone compared to the control group, respectively (P < 0.001). The inhibitory effect of cisplatin was enhanced with lycopene addition by declining the cell viability to 37.4% (P < 0.0001). Lycopene treatment significantly increased Bax expression (P < 0.0001) and decreased Bcl-2 expression (P < 0.0001) in HeLa cells. Furthermore, lycopene markedly activated the Nrf2 expression (P < 0.001) and suppressed the NF-kB signaling pathway (P < 0.0001). Conclusion: Lycopene increases the sensitization of cervical cancer cells to cisplatin via inhibition of cell viability, up-regulation of Bax expression, and down-regulation of Bcl-2 expression. Furthermore, the anticancer effect of lycopene might be also associated with suppression of NF-kB-mediated inflammatory responses, and modulation of Nrf2-mediated oxidative stress. The results of the present study suggest that lycopene and concurrent cisplatin chemotherapy might have a role in improving the treatment of cervical cancer. [ABSTRACT FROM AUTHOR]