Abstract: Objective To compare the effects of HCV core of different genotypes on cell apoptosis of HepG2 cell. Methods The plasmid pcDNA3.1/myc-His (－)-core of genotype 6a [pCore (6a)] was constructed. And then pCore (1b), pCore (3a), pCore (6a) and negative control pcDNA3.1/myc-His (－) (pNC) were transiently transfected into HepG2 cells respectively. Flow cytometry was used to observe cell apoptosis post 48 hours while the mRNA levels and activities of caspase-3 were detected by Real-time PCR and caspase-glo 3/7 luminometer respectively. Then, compare the different effects of HCV core of different genotypes on cell apoptosis were compared. Results The plasmid pcDNA3.1/myc-His (－)-core of genotype 6a [pCore(6a)] was successfully constructed. Compared with control group, the number of Annexin V-positive cells were all decreased in core (1b), core (3a) or core (6a) expressed HepG2 cells, among which the effect of core (6a) was more remarkable. Meanwhile, the mRNA levels and activities of caspase-3 were all reduced in core (1b), core (3a) or core (6a) expressed HepG2 cells. Moreover, compared with core (1b) and core (3a), the effect of core (6a) is more significant in terms of caspase-3 mRNA level, but not caspase-3 activity. Conclusions Different genotypes of HCV core have different effects on cell apoptosis. Inhibitory effect of genotype 6a core on apoptosis is more significant. HCV core protein of genotype 6a may be easier to cause liver cancer, which needs further study.