Studies have shown that soya consumption has been associated with low incidence of CVD. Because the chemical structures of soya isoflavones are similar to oestrogen, the beneficial outcome may be attributed to the oestrogenicity of these compounds. In this study, effect of the soya isoflavone genistein on the mRNA expression of apoA-1 in the human hepatoma HepG2 cell was investigated. Without oestrogen receptor (ER) α transfection, soya isoflavones in the physiological range had no effect on the apoA-1 transcription. Once ERα was ectopically expressed in these cells, soya isoflavone dramatically increased the apoA-1 mRNA abundance quantified by real-time PCR. ApoA-1-reporter assays with plasmid constructed from the 5′-flanking segment upstream to the coding region revealed that the transactivation of the apoA-1 promoter was induced by the soya isoflavone in HepG2 cells expressing ERα. This induction was reduced by the anti-oestrogen ICI 182780, but not the inhibitors of protein kinase (PK) C, PKA, or mitogen-activated PK. Based on the previously identified response elements on the promoter, a series of truncated promoter reporter plasmids were then constructed. An induction profile of genistein was built and insulin response core element at − 411 to − 404 appeared to be a potential site of interaction. This study illustrated that soya isoflavones at physiological concentrations could up regulate apoA-1 mRNA expression in ERα-transfected HepG2 cells.