Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), is characterized by chronic inflammation of the lower gastrointestinal tract with unknown etiology. In our previous study, NOD-like receptor 3 (NLRP3) inflammasome activation requiring the interaction of NLRP3 with NIMA Related Kinase 7 (NEK7) had been reported to regulate MODE-K cell pyroptosis and dextran sulfate sodium (DSS)-induced murine colitis. In the present study, miR-200c was closely related to IBD using weighted gene correlation network analysis (WGCNA). MicroRNA-200c (miR-200c) expression was down-regulated in IBD samples and negatively correlated with NLRP3. In MODE-K cells, miR-200c overexpression inhibited cellular inflammation; under adenosine triphosphate (ATP) and lipopolysaccharides (LPS) co-stimulation, miR-200c overexpression attenuated ATP and LPS-induced cell pyroptosis. In the DSS-induced IBD mice model, miR-200c overexpression alleviated DSS-induced IBD symptoms and improved physiological and biochemical indexes. Through direct targeting, miR-200c inhibited NEK7 expression. In MODE-K cells, NEK7 overexpression promoted cellular inflammation and ATP and LPS-induced cell pyroptosis; when co-transduced into MODE-K cells, NEK7 overexpression partially attenuated miR-200c agomir effects on cellular inflammation and ATP and LPS-induced cell pyroptosis. In conclusion, miR-200c, through targeting NEK7, could decrease cellular inflammation levels and NLRP3 inflammasome-related MODE-K cell pyroptosis in vitro and improve DSS-induced murine IBD symptoms in vivo.