Previous studies have shown that microRNA‐206 ( miR‐206) exhibits anti‐tumour properties in various tumours. Nevertheless, diagnostic significance of miR‐206 in oral cancer is still poorly known. Our research was carried out to explore the performance of miR‐206 in the diagnosis of oral cancer. Quantitative real‐time polymerase chain reaction (qRT‐PCR) method was adopted to measure the level of miR‐206 in serum specimens from oral cancer cases and control individuals. Chi‐square test was performed to analyse the correlation between miR‐206 level and clinicopathological parameters of the cases. Receiver operating characteristic (ROC) curve was constituted to assess diagnostic accuracy of miR‐206 in oral cancer. Serum miR‐206 level in oral cancer patients was significantly lower than that in control individuals ( P < .001). miR‐206 expression was obviously related to T classification ( P = .033), TNM stage ( P = .008) and lymph node metastasis ( P = .028). The area under the curve (AUC) of the ROC curve was 0.846 (95% CI = 0.797‐0.896, P < .001) with a specificity of 72.7% and a sensitivity of 81.2%. It revealed that miR‐206 might be a non‐invasive indicator in differentiating oral cancer cases from control individuals. Down‐regulation of miR‐206 is related to the development of oral cancer. Serum miR‐206 might be an effective indicator for early detection of oral cancer.