Background: Caries development in the teeth is multifactorial diseases where the environment, and the genetic factors play an important role in the onset and recurrence. Defensins are small, cationic, cysteine-rich peptides found to be active against microorganisms including bacteria, fungi and many non-enveloped and enveloped viruses. It play a significant role in defense against numerous pathogens, and they are deliberated part of the innate immunity. They have usually been considered to contribute to mucosal health. Defensin (DEFB1) gene polymorphisms may modulate human beta defensin (HBD-1) levels might be related to pathogenesis of numerous ailments. Aim: The present investigation was aimed to understand the association of two single-nucleotide polymorphisms (rs1799946 and rs11362) of DEFB1 gene with dental caries. Results: we could found that the single-nucleotide polymorphism (SNP) rs11362 is positively associated with the progression of dental caries in the tested population. Conclusion: our analysis possibly identified the accentuate relationship between dental caries and the SNP rs11362 polymorphism of the defensin gene (DEFB1), innate immune players in the oral area.