Background: Light chain3 is a sensitive autophagy-related protein distributed within the mammalian tissues. The role of LC3 localization in psoriasis pathogenesis is still poorly understood. Objective: This study aimed to investigate, for the first time up to our knowledge, the localization of Light chain3 (LC3) in the keratinocytes of psoriatic skin by immunohistochemical study. Materials and methods: This prospective case case-control study was carried out on 30 patients presented with chronic plaque psoriasis versus 30 age and gender-matched apparently healthy volunteers. Clinical data were collected and Psoriasis Area and Severity Index (PASI) was assessed. From all controls and cases (lesional and perilesional), skin biopsies were taken and the epidermis was assessed for histopathological changes and LC3 immunoreaction. Results: There was a highly significant difference (P<0.001) between the control skin and psoriatic skin (lesional and perilesional) regarding the epidermal LC3 localization. Nucleocytoplasmic LC3 localization was dominant in lesional skin specimens. Conclusion: Nucleocytoplasmic localization of LC3 in the keratinocytes of the psoriatic skin might play a pivotal role in psoriasis pathogenesis. This can open a new gate for target therapy in psoriasis.