Objective To explore the role of Adra1a in regulating the LPS-induced inflammation response in primary hepatocytes of lipopolysaccharide-binding protein knockout ( Lbp^{- / -}) mice. Methods Primary hepatocytes were extracted from WT and Lbp^{- / -} mice using a two-step perfusion method, and an inflammation model was established using LPS induction. Expression of Adra1a in primary hepatocytes of Lbp^{- / -} mice was suppressed by administering the inhibitor prazosin and transfection with si-Adra1a. The cells were divided into three groups under inhibitor conditions: control group A, LPS group A, and prazosin group. For siRNA transfection, cells were also divided into groups: control group B, LPS group B, si-NC group, and si-Adra1a group. WT primary hepatocytes were divided into two groups: control group (blank) and LPS group (12 h stimulation). Changes in the Adra1a response to LPS stimulation were verified by Western blot.Other method ologies, such as CCK-8, qRT-PCR, and Western blot assays, were used to confirm improvements in cell inflammation and the survival rate by prazosin and si-Adra1a. Results Significant elevation in Adra1a protein expression in Lbp^{- / -} primary hepatocytes was observed post-LPS stimulation (P<0. 01), whereas no notable change was found in the wildtype. A remarkable increase in the cell survival rate was noted in prazosin and si-Adra1a groups (P<0. 01, P<0. 05).Furthermore, prazosin and si-Adra1a groups exhibited significantly reduced expression of proinflammatory factors TNF-α and IL-1β (P<0. 01), p-p38, p-ERK, and p-JNK (P<0. 01), which are associated with cell damage and inflammation. Conclusions Following LPS stimulation, upregulation of Adra1a and proinflammatory cytokine expression was observed in Lbp^{- / -} primary hepatocytes. Specific downregulation of Adra1a expression using prazosin and si-Adra1a significantly decreased LPS-induced proinflammatory cytokines in Lbp^{- / -} primary hepatocytes. Adra1a is implicated in the regulation of the LPS-induced inflammation response in primary hepatocytes of Lbp^{- / -} mice.