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BACKGROUND Pneumonia, a severe infectious respiratory disease, is one of the leading causes of mortality and morbidity in children. Cbp/P300 interacting transactivator with Glu/Asp-rich carboxy-terminal domain 2 (CITED2) functions as a transcription cofactor, and plays critical roles in the development of embryonic and extra-embryonic tissues, including fetal lung maturation. The present study investigates the role of CITED2 in infantile pneumonia. METHODS The human fetal lung fibroblasts (MRC-5 and WI-38) were treated with lipopolysaccharides to induce cytotoxicity, and the cell viability was detected by MTT. Inflammation was evaluated by ELISA, and western blot was used to investigate the pyroptosis. RESULTS CITED2 was down-regulated in lipopolysaccharide-treated MRC-5/WI-38 cells. The over-expression of CITED2 protected MRC-5 and WI-38 cells from lipopolysaccharide--induced cytotoxicity by increasing the cell viability and decreasing LDH expression. CITED2 reduced the expression of TNF-α, IL-6, IL-1β in lipopolysaccharide-treated MRC-5/WI-38 cells. Lipopolysaccharide stimulated pyroptosis in MRC-5 and WI-38 cells through the up-regulation of NL+RP3, GSDMD-N, caspase-1, IL-1β and IL-18. However, CITED2 down-regulated the expression of NLRP3, GSDMD-N, caspase-1, IL-1β, and IL-18 protein in lipopolysaccharide-treated MRC-5/WI-38 cells. CITED2 also down-regulated the protein expression of p-p65 in lipopolysaccharide--treated MRC-5/WI-38 cells. CONCLUSION CITED2 exhibited anti-inflammatory effect on lipopolysaccharide-treated human lung fibroblasts and reduced pyroptosis through inactivation of NF-κB pathway.