The research aims to explore the roles and underlying mechanisms of microRNA-21 (miR-21) in lipopolysaccharide (LPS)-induced inflammation in MH7A cells. Cells were treated with LPS and/or transfected with miR-21 mimic/inhibitor or pc-sucrose nonfermentable 5 (SNF5). Cell viability was detected by CCK-8. ELISA and western blot were respectively conducted to measure the protein levels of pro-inflammatory factors, NF-κB or PTEN/PI3K/AKT key proteins and SNF5. miR-21/U6 was measured by qRT-PCR. The association between miR-21 and SNF5 was determined by luciferase reporter assay. Cell viability and the protein expression levels of interleukin-1β (IL-1β), IL-6, and p/t-p65, p/t-IκBα, p/t-PI3K, and p/t-AKT were significantly elevated by LPS, but with an inhibition of p-PTEN. Besides, LPS upregulated miR-21, whose overproduction or silence enhanced or alleviated the LPS stimulation on those elements above, respectively. miR-21 mimic notably inhibited SNF5, which was accelerated by miR-21 inhibitor, and abundant SNF5 abolished the effect of miR-21 mimic on cell viability, pro-inflammatory mediators, and sensitivity of signaling pathways, representing a negative relationship between them. miR-21 augmented LPS-induced inflammation response through activating NF-κB and PTEN/PI3K/AKT pathways by silencing SNF5 in MH7A cell line.