Toll like receptors (TLRs) are expressed in the skin and airway epithelial tissues, which are the most important sites of host‐pathogen interactions. TLRs recognize the three‐dimensional structure of pathogen associated molecules and are thus useful markers of the innate immune response. Here, we investigated the role of lipopolysaccharides (LPS) and monosodium urate (MSU) crystals in the activation of the TLR and Nod Like Receptors (NLR) pathways in human keratinocytes. Analysis of the inflammasome compounds revealed that NLRP3 and TLR4, both of which are components of inflammasome complexes involved in the activation of IL‐1β, were not expressed in keratinocytes. Transcriptomic analysis showed that combination of both MSU and LPS priming do not elicit significant result compare to MSU treatment that induced the expression of TLR2, IL‐6 and IL‐8/CXCL8 in the keratinocyte cell line HaCaT. Furthermore, MSU promoted the phosphorylation of Erk1/2 and MAPK14/p38α MAP kinases. We concluded that MSU stimulates a pro‐inflammatory response in keratinocytes via MAP Kinase pathway to induce production of IL‐8/CXCL8 and TLR2. This article is protected by copyright. All rights reserved.