<h4>Background</h4>This study examined the role of arecoline-induced zinc finger protein 582 (ZNF582) methylation via extracellular vesicles (EVs) in oral squamous cell carcinoma (OSCC) and its effect on PD-L1 expression through the interferon-induced protein with tetratricopeptide repeats 1 (IFIT1) pathway.<h4>Materials and methods</h4>EVs were isolated from SAS and TW2.6 cancer cell lines using ultracentrifugation and characterized using electron microscopy. The gene discussed is ZNF582; the disease is cancer.