Successive chromatography of EtOAc-soluble extracts of the fruiting body of Sparassis crispa (Wulf.) resulted in isolation of four new aromatic compounds, sparoside A (1) and sparalides A-C (3-5), two new naturally occurring compounds, 2 and 6, and eight known compounds, 7-14. The chemical structures were determined by interpretation of nuclear magnetic resonance and mass spectrometry spectroscopic data. Extract, solvent-soluble fractions of the extract, and all of the pure compounds isolated from the fractions were subjected to the mRNA expression assay for proprotein convertase subtilisin/kexin type 9 (PCSK9). Among them, sparoside A (1), hanabiratakelide A (8), adenosine (11), and 5α,6α-epoxy-(22E,24R)-ergosta-8(14),22-diene-3β,7β-diol (14) exhibited potent inhibitory activities on PCSK9 mRNA expression, with IC values of 20.07, 7.18, 18.46, and 8.23 μM, respectively (berberine, positive control, IC = 8.04 μM), suggesting that compounds 1, 8, 11, and 14 are suitable for use in supplements to the statins for hyperlipidemia treatments.