Therefore, the main objective of this study was to examine the potential association of single nucleotide polymorphisms (SNPs) in 3′ UTR of TLR7 gene (rs3853839) and TLR9 −1486 T/C (rs187084) with cancer susceptibility, clinicopathological features, prognosis, and overall survival (OS) of HPV-negative OSCC patients. The gene discussed is TLR9; the disease is cancer.