Cancer is one of the compelling and pegged disease battled by clinicians and researchers worldwide. Among different types of cancer, oral cancer holds the sixth position globally. With an escalating prevalence in Asian countries, India, China, and Pakistan constitute a large proportion of total incident of oral cancer patients in terms of new cases or deaths. This mounting prevalence is ascribed to poor oral hygiene and rampant use of substances earmarked as potential risk factors of the disease. Risk factors (dietary/lifestyle habits/occupational/environmental) trigger the activation of oncogenes, dysregulation of lncRNA and miRNA, and silence the tumor suppressor genes, which robustly contributes to the onset and progression of tumorigenesis in oral squamous cell carcinoma. Evidences suggest that specific carcinogens identified in tobacco and related products alter many cellular pathways predisposing to advanced stages of oral cancer. Long non-coding RNAs represent a broad group of heterogenous transcripts longer than 200 nucleotides which do not translate to form functional proteins. They regulate various cellular pathways by specifically interacting with other RNAs, DNA, and proteins. Their role in the pathogenesis of OSCC and other cancer is still being debated. In this review, we discuss the molecular insights of significant lncRNAs involved in some crucial deregulated pathways of tobacco associated OSCC. The implications and challenges to harness the potential of lncRNAs as biomarkers in early diagnosis and targeted treatment have also been analyzed.

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