Background Oral squamous cell carcinoma causes a significant proportion of global cancer morbidity and mortality. The aim of this study is to investigate whether the exhaled breath test can be a new, non-invasive, and effective method for diagnosing oral squamous cell carcinoma. Methods A comparative analysis of exhaled breath between patients with oral squamous cell carcinoma (OSCC) and healthy controls (HC) was performed with the Twin Breasor II™, a simple gas chromatography system. Results Both hydrogen sulfide (H2S) and methyl mercaptan (Ch3SH) were significantly higher in the OSCC group than in the HC group. The total sulfur concentration was also higher in the OSCC group, but there was no significant difference in the ratio of Ch3SH to H2S between the two groups. Using logistic regression, we constructed a new variable with an area under the curve (AUC) of 0.740, 68.0% sensitivity, and 72.0% specificity. Conclusions Exhaled gas analysis via simple gas chromatography can potentially serve as an accessory non-invasive method for OSCC diagnosis.