Abstract: Oral squamous cell carcinoma (OSCC ), one of the cancers originating from the epithelium lining the upper gastrointestinal system, is a serious global health issue. Despite improvements in diagnosis and novel tailored treatments, it is still considered one of the most prevalent cancers. Although systematic treatment methods, including surgery, radiation therapy and chemotherapy, have achieved reduced mortality and higher survivor rates, a significant proportion of OSCC patients undergoing oral treatment develop metastasis and recurrence.Therefore, it is essential to identify biomarkers for early diagnosis, prognosis prediction, treatment response and overall survival of OSCC. The current research aimed to identify the dysregulated miRNAs in cancerous tissues and plasma of OSCC patients compared to adjacent healthy tissue and plasma of normal control and also to identify whether the dysregulated miRNAs are present in the plasma of post-operative OSCC patients showing recurrence and no recurrence. For this study, blood samples, biopsies of normal and tumour tissue and FFPE blocks were taken from eleven OSCC patients with and without recurrence in the oral cavity and one normal control individual. A microRNA library was created after total RNA and microRNA isolation from these materials. This experimental study used next-generation sequencing (NGS ) to identify the differentially expressed miRNAs in tissues and serum of OSCC patients and normal healthy control. The prominently dysregulated miRNAs were validated with qRT-PCR. By analysing the expression of their mRNA targets and performing a pathway analysis, we could narrowly concentrate on the expression mechanism of miRNA profiles linked with oral cancer recurrence. This research discovered differentially expressed miRNAs by next-generation sequencing (NGS) using paired tissue and serum samples from OSCC patients and matched controls. During tissue profiling, 317 miRNAs were discovered while 164 unique miRNAs were identified in serum plasma samples. When we examined the miRNA expression in tumours and healthy tissues, we discovered 22 differentially expressed miRNAs (11 miRNAs down-regulated and 11 up-regulated; false discovery rate 0.05). Our research revealed that specific miRNAs, including hsa-miR-142-3p, hsa-miR-32-5p, has-miR-21, hsa-miR-141, and hsa-miR-29c were up-regulated in tumour tissues more frequently as compared to normal healthy tissues. Meanwhile, hsa-miRNA 375, hsa-miRNA 199a-5p, hsa-miRNA 99a, let-7a, and hsa-miRNA 199a-3p were all found to be more frequently downregulated in tumour tissues. Out of these 22 miRNAs, up-regulation of hsa-miR-32-5p, and down-regulation of hsa-miR-375 were identified in the pre-operative serum plasma of the same group of OSCC patients. Among these patients, 4patients with hsa-miR-375 downregulation developed early recurrence, 3 patients with miR-32-5p developed late recurrence and 4 patients with other miRNA dysregulation pattern showed no recurrence post-operatively till date. In this study, hsa-miR-375 and hsa-miR-32-5p appeared as the most predominant miRNAs associated with post-surgical recurrence. Our results suggest the potential of utilizing these circulating plasma miRNAs as noninvasive biomarkers associated with post-surgical recurrence risk in OSCC patients.