Mushroom is known for anti-inflammatory and anti-oxidative potential. This study provides evidence that theinhibitory effect of mushroom on the expression of pro-inflammatory cytokines in human keratinocytes, HaCaT cells. To definethe underlying mechanisms of action, tumor necrosis factorα/IFNγ-activated human keratinocytes model was used. Mushroomsignificantly inhibited the expression of cytokines in HaCaT cells. Taken together, the results demonstrate that mushroom inhibitedinflammtion, suggesting that mushroom (DW extract: Grifola frondosa Cordyceps militaris), (Ethanol extract: Ganoderma lucidum,Lentinus edodes, Cordyceps militaris, Flammulina velutipes) might be a candidate for the treatment of skin inflammation.