Objective <p>This study aimed to investigate the potential mechanism of circRNA TEAD1 (circTEAD1) regulating autophagy and its role in liver ischemia–reperfusion injury (LI/RI).</p> Methods <p>An in vitro LI/RI model was established using AML12 cells subjected to hypoxia/reoxygenation (H/R). Cells were transfected with plasmid vectors targeting circTEAD1, miR-92b-3p, or TLR4 expression. Cell viability was assessed by MTT, apoptosis by flow cytometry, and apoptosis-related and autophagy-related protein levels by Western blot. Putative miRNAs targeting circTEAD1 were identified using the starBase database, and the top 10 candidate miRNAs were subjected to RT‑qPCR validation. A dual-luciferase reporter assay was performed to confirm the targeting relationship between miR-92b-3p and circTEAD1 or TLR4. Liver tissue injury, apoptosis, and autophagy in LI/RI mice were evaluated after tail vein injection of recombinant lentiviral vectors that modulated circTEAD1, miR-92b-3p, or TLR4.</p> Results <p>In H/R‑treated AML12 cells, circTEAD1 and TLR4 expression were significantly upregulated whereas miR-92b-3p was downregulated. Knockdown of circTEAD1 increased cell viability and decreased apoptosis and autophagy; however, these effects were reversed by miR-92b-3p inhibition. Similarly, overexpression of miR-92b-3p promoted cell viability and suppressed apoptosis and autophagy, effects that were reversed by TLR4 overexpression. circTEAD1 directly bound miR-92b-3p, and miR-92b-3p directly targeted TLR4. In vivo, inhibition of circTEAD1 attenuated liver injury, apoptosis, and autophagy in LI/RI mice through the miR-92b-3p/TLR4 axis.</p> Conclusion <p>Downregulation of circTEAD1 mitigates LI/RI by inhibiting autophagy via the miR-92b-3p/TLR4 axis.</p>