While several modes of therapeutic approaches for cancer remained highly debatable, Clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated protein 9 (CRISPR/Cas9) tool with enhanced genome editing capabilities has shown promising outcome in recent years. Studies have established the importance of this system in identifying the genes which are critical to a particular type of cancer. According to Cheong and colleagues, CRISPR/Cas9 system is having profound efficacy in identifying genes associated with oral cancer pathobiology. In another study, 4NQO-induced carcinogenic processing was effectively identified by CRISPR/Cas9 tool. Moreover, in human trial similar results were evident from lung cancer patients. Together, all such novel contributions of CRISPR/Cas9 system have made it a research focus of present time and also established the efficacy of CRISPR/Cas9 system to find out the target for specific set of genes responsible for causing cancer. In Indian perspective, North-East region is having traditional betel-nut chewing habits, which has been reported to be associated with increasing trend of oral carcinogenic processing. Hence, CRISPR/Cas9 system could assist in tracking carcinogenic progression and identifying the expression patterns of genes, which in turn could help to specify potential targets to enhance the global therapeutic possibilities. In the present study, we have discussed all the therapeutic aspects of CRISPR/Cas9 system and presented a rational discussion on the efficacy of CRISPR/Cas9 system in regulation or modification of carcinogenic progression with special emphasis on oral precancerous and cancerous stages.