Resatorvid (TAK-242), a selective TLR4 signaling inhibitor, significantly enhanced 3HP's inhibitory effect on TLR4, further indicating that 3HP may block the NF-κB p65/NLRP3/GSDMD signaling pathway by inhibiting TLR4 activation in response to LPS stimulation.<h4>Conclusions</h4>Our results demonstrated that 3HP mitigates LPS-induced ALI by inhibiting TLR4 activation-mediated NF-κB p65/NLRP3/GSDMD signaling. Here, TLR4 is linked to acute respiratory distress syndrome.