Objective To explore the effects and mechanism of the alcohol extract of Hemerocallis citrina Baroni (HCE) and its prescriptions Xinning Granules (XN) on lipopolysaccharide (LPS) induced neuroinflammation in BV2 cells. Methods BV2 cells in the logarithmic phase were divided into the control group, LPS group, HCE group (150, 300, 600 μg/mL), and XN group (15, 30, 60 mg/mL). The cell viability in HCE and XN were detected by CCK-8 assay. The content of NO in the cell supernatant was detected by the Griess method. Cell apoptosis was detected by Hoechst staining. The levels of TNF-α, IL-1β and IL-6 in the supernatant were detected by ELISA. The expression levels of IL-1β, IL-6, CD86, iNOS, COX2, NF-κB, TGF-β1, Arg-1, STAT6 and AKT1 mRNA in cells were detected by RT-qPCR. Results The CCK-8 results showed that HCE at concentrations below 800 μg/mL and XN at concentrations below 70 mg/mL had no toxic effect on BV2 cells (P<0.01). 1 μg/mL LPS significantly increased the NO content in the cell supernatant, HCE and XN could inhibit NO production (P<0.01).In addition, HCE and XN could significantly inhibit LPS-induced apoptosis and reverse the upregulation of TNF-α, IL-1β and IL-6 levels (P<0.05). Compared with the LPS group, HCE and XN could down-regulate the mRNA expression levels of M1 phenotypic genes (IL-1β, IL-6, CD86, iNOS, COX2, TLR4, NF-κB) and up-regulate the mRNA expression levels of M2 phenotypic genes (TGF-β1, STAT6, AKT1) (P<0.05), HCE could also up-regulate Arg-1 and IL-4 gene expression (P<0.05). Conclusions HCE and XN can inhibit the LPS-induced neuroinflammatory response by differentially regulating the TLR4/NF-κB and IL-4/STAT6 pathways.