Ischemic brain injury often results in irreversible pyroptosis of neurons. Sevoflurane (Sevo) post-treatment exerts an alleviative role in neuroinflammation.This work evaluated the mechanism of Sevo post-treatment in oxygen-glucose deprivation (OGD)-induced pyroptosis of rat hippocampal neurons.Rat hippocampal neuron cell line H19-7 was treated with OGD, followed by post-treatment of 2% Sevo. The expression patterns of MAF bZIP Transcription Factor B (Mafb) and dual-specificity phosphatase 14 (DUSP14) were determined via quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting methods. H19-7 cell viability and the release of lactate dehydrogenase (LDH) were examined via cell counting kit-8 and LDH assay kit. Levels of pyroptosis-related proteins and cytokines NOD-like receptor family, pyrin domain containing 3 (NLRP3), N-term cleaved Gasdermin-D (GSDMD-N), cleaved-caspase-1, interleukin (IL)-1β, and IL-18 were also examined. The binding relation between Mafb and the DUSP14 promoter were detected. Besides, the roles of Mafb/DUSP14 in OGD-induced pyroptosis of rat hippocampal neurons were investigated through functional rescue experiments.Mafb and DUSP14 expression levels were decreased in OGD-induced hippocampal neurons. Sevo post-treatment up-regulated Mafb and DUSP14, facilitated H19-7 cell viability, inhibited LDH release, and reduced levels of NLRP3, GSDMD-N, cleaved-caspase-, IL-1β, and IL-18. Mafb increased DUSP14 expression via binding to the DUSP14 promoter. Repressing Mafb or DUSP14 exacerbated pyroptosis of hippocampal neurons.Sevo post-treatment increased Mafb and DUSP14 expressions, which repressed OGD-induced pyroptosis of hippocampal neurons.Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.