Our previous study showed that Semen sojae germinatum (SSG), a soy-derived Chinese medicinal material, have potential benefits for knee osteoarthritis (OA). This study was undertaken to identify the major effective sub-fraction of SSG. The 95% ethanol extract of SSG was successively fractionated into petroleum ether, ethyl acetate, n-butanol and aqueous fractions. Then we examined the effect of fractions on the inflammatory response and cell proliferation of primary human osteoarthritic chondrocytes stimulated by interleukin (IL)-1β, a recognized and common inducer of OA in vitro. Results showed that the petroleum ether, ethyl acetate and n-butanol extracts of SSG promoted cell-proliferation measured by MTT [3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazoliumbromide] assay, increased the transcript levels and nuclear translocation of cyclin D1, and inhibited the production of pro inflammatory mediator prostaglandin (PG)E 2 and nitric oxide (NO) induced by IL-1β in human OA chondrocytes, suggesting SSG extracts possessed chondro protective and anti-inflammatory properties. The ethyl acetate fraction was superior to other fractions. These data indicated SSG extracts might become a potential treatment option for humans with OA.