Objective: The objective of this research was to identify and replicate the participation of KLK4 gene polymorphisms in the susceptibility to dental decay. Methods: A total of 200 patients were recruited using ICDAS criteria - 100 of them with dental caries and 100 with no history of the disease. Buccal cells were collected and the DNA was extracted and amplified using PCR. Results: During the descriptive analysis, the variables ethnicity, biofilm, and gingivitis and the markers rs2242670 and rs2978642 were statistically significant. In the multivariate analysis, the marker rs2242670 and the variable biofilm maintained statistical significance. Conclusion: Genetic variations in the KLK4 gene may contribute to dental decay.