Studies have indicated a correlation between a high level of urinary lignans and isoflavonoid phytoestrogens, particularly genistein, and a low incidence of hormone-dependent cancers, such as breast and prostate cancer. Previously it has been observed that a vegetarian diet is associated with high plasma levels of sex hormone-binding globulin (SHBG), reducing clearance of sex hormones and probably risk of breast and prostate cancer. In the present study we investigated the in vitro effect of genistein on the production of SHBG by human hepatocarcinoma (Hep-G2) cells in culture and its effect on cell proliferation. We found that genistein not only highly significantly increases the SHBG production by Hep-G2 cells, but also suppresses the proliferation of these cancer cells already at a stage when SHBG production continues to be high. We conclude that, in addition to the lignan enterolactone, the most abundant urinary isoflavonoid genistein stimulates SHBG production and inhibits Hep-G2 cancer cell proliferation.