Medicinal mushroom is a prolific source of secondary metabolites with excellent biological activities. In this study, four new fluorenone derivatives, soloniensis A - D (1 - 4) were isolated from the rice-fermented mycelia of the medicinal mushroom Piptoporus soloniensis (Dubois:Fr.) Pilat. Their structures were established through extensive spectroscopic analyses including HR-ESI-MS, 1D and 2D NMR. The anti-inflammatory activity in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophage cells demonstrated that fluorenones 1-4 exhibited significant anti-inflammatory activity with IC50 values ranging from 7.92 ± 0.61 to 18.15 ± 0.71 μM.