MutT Homolog 1 (MTH1) prevents the incorporation of oxidized nucleotide triphosphates into genomic DNA as an antioxidant defense mechanism. The induced expression of MTH1 in psoriatic skin highlights the altered redox regulation and supports the idea of targeted intervention. Thus, MTH1 inhibition can be a novel promising treatment modality for psoriasis. Mass spectrometry-based proteomics was used to understand the MTH1i-induced molecular alterations in human keratinocytes. The expression of identified candidate proteins and MTH1 were further validated using quantitative real-time PCR.