β-Hydroxy-β-methylglutaryl coenzyme A reductase(HMG-CoA reductase, E.C. 1.1.1.34) is known to be rate-limiting enzyme in cholesterol biosynthesis. HMG-CoA reductase inhibitor is very useful in the remedy or precaution of hyperlipidemia. The methanol extracts of Pholiota adiposa ASI 24018 showed the highest HMG-CoA reudctase inhibitory activity of 55.8%. The HMG-CoA reductase inhibitor of Pholiota adiposa ASI 24018 was maximally extracted when it was treated with methanol at 30℃ for 12hrs. After purified the HMG-CoA reductase inhibitor by systematic solvent extraction, LH-20 gel column chromatography and RP-HPLC, finally obtained the HMG-CoA reductase inhibitor with an activity of IC50 6.8ug. Molecular weight of the purified HMG-CoA reductase inhibitor was 765.4Da by LC-Mass, NMR, FT-IR, UV spectrometry.