For oral cancer, one of the most formidable challenges confronting humanity,104 missense mutations, single nucleotide polymorphisms, and C > T transitions emerge as the prevailing single nucleotide variation categories, with RANBP2 and SENP6 exhibiting the highest single nucleotide variation frequencies, among 15 SUMOylation regulatory factors examined in 323 cases of oral squamous cell carcinoma with an additional 32 cases representing normal tissue, as well as 96 cases of single nucleotide variations of oral squamous cell carcinoma. This evidence concerns the gene SENP6 and oral cavity squamous cell carcinoma.