Circular RNAs (circRNAs) play a key part in the progression of oral squamous cell carcinoma (OSCC). However, the role of circ-BNC2 (circRNA ID hsa_circ_0086414) in OSCC progression is still unclear.Plasmid transfection was used to induce overexpression of circ-BNC2. RNA expression of circ-BNC2, microRNA-142-3p (miR-142-3p) and GNAS complex locus (GNAS) was detected by quantitative real-time polymerase chain reaction. Protein expression was assessed by western blot assay or immunohistochemistry assay. Cell proliferation was investigated by 3-(4,5-dimethylthazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, colony formation assay and flow cytometry analysis. Cell migratory and invasive abilities and cell apoptosis were assessed by transwell assay and flow cytometry analysis, respectively. Oxidative stress was evaluated by superoxide dismutase activity detection assay, lipid peroxidation malondialdehyde assay and cellular reactive oxygen species assay. The binding relationship between miR-142-3p and circ-BNC2 or GNAS was proved by dual-luciferase reporter assay and RNA immunoprecipitation assay. The impacts of circ-BNC2 overexpression on tumor growth in vivo were unveiled by a xenograft mouse model assay.Circ-BNC2 expression was downregulated in OSCC tissues and cells when compared with adjacent healthy tissues and normal human oral keratinocytes. Circ-BNC2 overexpression repressed the proliferation, migration and invasion of OSCC cells but induced cell apoptosis and oxidative stress. Additionally, circ-BNC2 overexpression inhibited tumor growth in vivo. Furthermore, circ-BNC2 bound to miR-142-3p, and miR-142-3p targeted GNAS. MiR-142-3p mimic attenuated circ-BNC2 overexpression-mediated effects on the proliferation, migration, invasion, apoptosis and oxidative stress of OSCC cells. The regulation of miR-142-3p in OSCC cell tumor properties involved GNAS. Further, circ-BNC2 introduction promoted GNAS expression by inhibiting miR-142-3p.Circ-BNC2 suppressed OSCC malignant progression by upregulating GNAS expression in a miR-142-3p-dependent manner, which suggested that circ-BNC2 might be a novel target for OSCC therapy.© 2023 Wiley Periodicals LLC.