Caspases (CASP) are intracellular proteases that play roles as mediators of apoptosis. Activation of caspase 3 is enhanced in chronic periodontitis. Thus, we hypothesized that single nucleotide polymorphisms (SNPs) of CASP genes might be associated with this condition in the Korean population. To investigate whether such polymorphisms might be involved in the development of periodontal disease, 51 patients and 33 control subjects were assessed. A total of 201 CASP gene SNPs were analyzed with genotypes being determined using and Axiom(TM) genome-wide human assay. SNPStats and SPSS 18.0 were used for the analysis of genetic data and logistic regression models were utilized to evaluate odds ratios, 95% confidence intervals, and P values. Of the 201 SNPs, only three (rs12108497, rs4647602, and rs113420705, all in the CASP3 gene) were significantly associated with chronic periodontitis (P < 0.05). The minor allele frequencies of these SNPs were higher in the patient group than in the control group. In addition, the TC and GT haplotypes formed by rs4647602 and rs113420705 were found to be associated with chronic this disease (TC haplotype, P = 0.0039; GT haplotype, P = 0.002). These results suggest that CASP3 gene polymorphisms may be associated with susceptibility to periodontal disease in the Korean population.