MicroRNAs (miRNAs) are small regulatory non-coding RNAs for which altered expression in cancers can serve as potential biomarkers for diseases. We here investigated whether circulating miRNAs can serve as biomarkers for predicting post-operational recurrence of oral squamous cell carcinoma (OSCC) in patients. Plasma samples from 8 Danish OSCC patients were collected before, and one year after surgical operation, as well as from 3 Danish healthy controls and subjected to miRNA profiling by next generation sequencing. Disease recurrence did not occur in the 8 patients when the post-operative plasma samples were collected. Based on the sequencing data, three up-regulated miRNAs (miR-148a-3p, miR-26a-5p and miR-21-5p) and three down-regulated miRNAs (miR-375, miR-92b-3p and miR-486-5p) in the OSCC samples compared to healthy controls were selected for qRT-PCR validation in a Chinese cohort of 20 plasma samples collected before, and 9-12 months after surgical operation, and 18 healthy controls. Disease recurrence had occurred in 8 out of the 20 Chinese patients at the time their post-operative plasma samples were collected. The results of qRT-PCR showed that down-regulation of miR-486-5p, miR-375 and miR-92b-3p were highly associated with OSCC recurrence. This study indicates that the plasma miRNA profile is altered in OSCC during its progression and can be used to monitor the likelihood of OSCC recurrence in patients after surgery.