The purpose of this study was to test the association between single-nucleotide polymorphisms (SNPs) of 8-oxoguanine DNA glycosylase (OGG1) gene and susceptibility to pancreatic cancer (PC). A total of 347 PC patients and 364 healthy subjects were enrolled in this case-control study. The c.269C>A genetic variant was investigated using the created restriction site-polymerase chain reaction method. The c.627T>C genetic variant was identified by the polymerase chain reaction-restriction fragment length polymorphism method. Our data indicated that the alleles and genotypes frequencies of these two SNPs were statistically different in PC cases and controls. As for c.269C>A, the AA genotype was statistically associated with decreased PC susceptibility compared to CC wild genotype (odds ratio (OR) = 0.44, 95% confidence interval (CI) 0.27-0.73, P = 0.001). As for c.627T>C, statistically significant decreased PC susceptibility was detected in CC genotype compared to TT wild genotype (OR = 0.57, 95% CI 0.35-0.94, P = 0.028). The allele A of c.269C>A and allele C of c.627T>C might be associated with a protection from PC (for c.269C>A, A versus (vs.) C, OR = 0.69, 95% CI 0.55-0.86, P < 0.001; for c.627T>C, C vs. T, OR = 0.72, 95% CI 0.58-0.91, P = 0.005). Results from this study indicate that the c.269C>A and c.627T>C SNPs of OGG1 gene are associated with PC susceptibility in Chinese Han ethnicity.