We investigated whether the C1245G polymorphism of human 8-oxoguanine glycosylase 1 (hOGG1) gene confers the susceptibility to systemic lupus erythematosus (SLE) occurrence of lupus nephritis and affects the plasma level of 8-hydroxy-2'-deoxyguanosine (8-OHdG) in patients with SLE. A total of 45 healthy controls and 85 SLE patients were recruited. The C1245G polymorphism of the hOGG1 gene was determined by direct sequencing. The frequency of occurrence of the hOGG1 1245 GG genotype in SLE patients was 31.8% (27/85), which is lower than that of healthy controls of 53.3% (24/45). Thirty-three (33/85, 38.8%) SLE patients developed lupus nephritis. Significantly, SLE patients harboring the hOGG1 1245 GG genotype had a higher incidence to develop lupus nephritis than did those harboring the hOGG1 1245 CC or CG genotype (15/27, 55.6% vs.18/58, 31.0%, p = 0.031). Divided into subgroups, SLE patients harboring the hOGG1 1245 GG genotype had the highest plasma levels of 8-OHdG among patients with all genotypes, with regard to the coexistence of lupus nephritis (p = 0.020, ANOVA), including those with nephritis harboring the hOGG1 1245 CC or CG genotypes (p = 0.037), those without nephritis harboring the hOGG1 1245 GG genotype (p = 0.050), and those without nephritis harboring the hOGG1 1245 CC or CG genotype (p = 0.054). We conclude that the C1245G polymorphism of hOGG1 may be one of the factors that confer the susceptibility to lupus nephritis and modulate the plasma level of 8-OHdG in patients with SLE.