〔Abstract〕 Objective To investigate the reversal of drug resistance of drug-resistant hepatoma cell line HepG2/DDP by emetine and its mechanism. Methods The drug-resistant hepatoma cell line HepG2/DDP was established by high-dose cisplatin(DDP) shock combined with low-dose continuous induction. Reverse virtual screening, molecular docking, surface plasmon resonance(SPR) and Western blot assays were employed to explore the target of emetine. The target was validated by transfection assayin vivo. The inhibitory effect of emetine combined with DDP on the proliferation of HepG2/DDP cells was detected by cytotoxicity assay. The sensitization effect of emetine was verified by flow cytometry, and the expression of the apoptosis related proteins BCL2, Bax and Cleaved-caspase-3 were analyzed by Western blot. Results Emetine enhanced the sensitivity of HepG2/DDP cells to DDP and reduced the resistance index(RI) from 3.69 to 0.93. Reverse virtual screening, molecule docking and SPR results showed that emetine can stably bind to PARP-1. Western blot assays showed that emetine had a potent enzymatic inhibitory activity against PARP-1in vivo. Furthermore, emetine's potentiation of DDP in HEPG2/DDP cells nearly disappeared when the cells were transfected with siRNAs against PARP-1. Flow cytometry showed that emetine could enhance the proapoptotic effect of DDP on HepG2/DDP cells. Conclusion Emetine can enhance the sensitivity of HepG2/DDP cells to DDP, and its mechanism may be related to its inhibition of PARP-1.