Purpose Ultraviolet irradiation is known to cause oxidative DNA damage and is thought to be a major factor implicated in the pathogenesis of pterygium. The highly mutagenic 8-hydroxy-2 0 -deoxyguanosine, a marker for the evaluation of photo-oxidative DNA damage, can be repaired by human 8-oxoguanine glycosylase I (hOGG1). A transition of C to G at nucleotide position 1245 in exon 7 of the hOGG1 gene is associated with the substitution of cysteine for serine at codon 326. In this study, we investigated the association of the hOGG1 Ser326Cys polymorphism with pterygium in a Chinese population. Methods In all, 70 patients and 86 controls were enrolled in this study. The Ser326Cys polymorphism was determined by the polymerase chain reaction-restriction fragment-length polymorphism analysis. The association between this genetic polymorphism and risk of pterygium was examined by w 2 -test and logistic regression. Results The allelic frequencies for the Ser and Cys variants of hOGG1 gene were not significantly different between the two groups. However, when compared with Ser/ Ser and Ser/Cys genotypes combined, we found that the homozygous Cys/Cys genotype was more prevalent in pterygium patients than controls (P ¼ 0.024) with the odds ratio being 2.2 (95% CI: 1.1-4.5). In the pterygium group, the mean age of patients with the Cys/Cys genotype was younger than those with the other two genotypes (P ¼ 0.025). Conclusions Our findings suggest that the 1245C-G transition in exon 7 of the hOGG1 gene, which results in Ser326Cys substitution of the enzyme, might play a role in the susceptibility of humans to pterygium.