The neuroprotective property of quercetin is well reported against hypoxia and ischemia in past studies.This property of quercetin lies in its antioxidant property with blood-brain barrier permeability and anti-inflammatory capabilities.μ-Calpain,a calcium ion activated intracellular cysteine protease causes serious cellular insult,leading to cell death in various pathological conditions including hypoxia and ischemic stroke.Hence,it may be considered as a potential drug target for the treatment of hypoxia induced neuronal injury.As the inhibitory property of μ-calpain is yet to be explored in details,hence,in the present study,we investigated the interaction of quercetin with μ-calpain through a molecular dynamics simulation study as a tool through clarifying the molecular mechanism of such inhibition and determining the probable sites and modes of quercetin interaction with the μ-calpain catalytic domain.In addition,we also investigated the structure-activity relationship of quercetin with μ-calpain.Affinity binding of quercetin with μ-calpain had a value of –28.73 k J/mol and a Ki value of 35.87 μM that may be a probable reason to lead to altered functioning of μ-calpain.Hence,quercetin was found to be an inhibitor of μ-calpain which might have a possible therapeutic role in hypoxic injury. The neuroprotective property of quercetin is well reported against hypoxia and ischemia in past studies. This property of quercetin lies in its antioxidant property with blood-brain barrier permeability and anti-inflammatory capabilities. Μ-Calpain, a calcium ion activated intracellular cysteine ​​protease causes serious cellular insult, leading to cell death in various pathological conditions including hypoxia and ischemic stroke .ence, it may be considered as a potential drug target for the treatment of hypoxia-induced neuronal injury. As the inhibitory property of μ-calpain is yet to be explored in details, hence, in the present study, we investigated the interaction of quercetin with μ-calpain through a molecular dynamics simulation study as a tool through clarifying the molecular mechanism of such inhibition and determining the probable sites and modes of quercetin interaction with the μ -calpain catalytic domain. In addition, we also investigated the structure-activity relationship of quer cetin with μ-calpain. Affinity binding of quercetin with μ-calpain had a value of -28.73 kJ / mol and a Ki value of 35.87 μM that may be a probable reason to lead to altered functioning of μ-calpain .ence, quercetin was found to be an inhibitor of μ-calpain which might have a possible therapeutic role in hypoxic injury.