<p>Acute ischemic stroke (AIS) is a medical emergency stemming from a reduction in cerebral blood supply, leading to neuronal injury. LINC00265 may emerge as a highly promising biomarker for stroke. The aim of this investigation was to investigate the clinical and prognostic significance of LINC00265 in AIS, as well as to elucidate the molecular mechanisms through which LINC00265 influences AIS. Blood samples were collected from 131 AIS patients. qRT-PCR was employed to measure the expression levels of LINC00265. The diagnostic and prognostic value of LINC00265 were evaluated using ROC curve and Kaplan–Meier survival curves, respectively. To establish an in vitro model of AIS, HCMIEC/D3 cells were subjected to OGD/R treatment. Cell proliferation was assessed using CCK-8 assay. The concentrations of TNF-α, IL-6, IL-1β, IL-4, and IL-10 were measured using ELISA kit. The protein expression levels of VCAM-1 and ICAM-1 were detected by Western blot analysis. The expression of LINC00265 was found to be significantly downregulated in AIS patients and strongly correlated with disease severity. The reduced expression of LINC00265 exhibited considerable significance for both diagnosis and prognosis prediction of AIS. At the mechanistic level, LINC00265 mitigated OGD/R-induced cellular injury by modulating the miR-155-5p/TRIM32 axis. Therefore,&#xa0;overexpression of LINC00265 may potentially suppress disease progression in AIS by regulating miR-155-5p/TRIM32 axis.</p> Graphical Abstract <p></p>