Oral Squamous Cell Carcinoma (OSCC) is the most common form of Head and Neck cancers. Recently, the focus has been given to the role of bacterial microbiota causing periodontal diseases in increasing the risk of developing OSCC. To investigate the potential role of microbiome dysbiosis in predicting the oral tumuorigenesis. Thirteen representative samples out of 166 collected clinical specimens were subjected for microbiome sequencing analysis according to the demographic data of the recruited individuals. The samples represented 3 groups; OSCC patients (n=4), patients with non-malignant oral diseases (n=3) and apparently healthy individuals (n=7). Small fragment library of 16S rRNA amplicon at variable region (V3-V4) was constructed on the Illumina NovaSeq sequencing platform. Version QIIME2 software with implemented DADA2 plugin was used for the paired-end reads obtained by sequencing, splicing, filtering and noise reduction. The effective data obtained was subjected to species annotation and abundance analysis to reveal the species composition of the samples by the identification of the bacterial Amplicon Sequence Variants (ASVs). The results revealed that Porphyromonas, Fusobacterium, Leptotrichia, Haemophilus, Prevotella, Veillonella, Capnocytophaga, and Streptococcus were among the most prevalent genera in oral cancer samples in comparison to either the healthy or non-malignant counterparts.  The dysbiosis of Porphyromonas, Prevotella, and Veillonella was markedly identified among the examined groups and, therefore, could be possible predictor of oral carcinogenesis. However, further large-scale microbiome analysis is requested to establish the association.