The X-ray repair cross-complementation group 1 (XRCC1) protein plays an important role in base excision repair. A high level of XRCC1 mRNA and/or protein has been found in rat and baboon brains. An exon 10 variant at codon 399 of XRCC1 leads to an Arg to Gln amino acid change. The 399Gln allele is associated with an increased risk of several types of cancers, increased DNA adducts and chromosomal changes; therefore, it appears that the 399Gln allele may alter the role of the XRCC1 protein in DNA repair. The present case-control study was performed on 303 (223 males, 80 females) in-patients with chronic schizophrenia and 303 healthy blood donors matched to the patients by age (+/-5 years) and gender. The XRCC1 genotypes were determined using a PCR-based method. Heterozygosity (OR=1.48, 95% CI: 1.05-2.09) and homozygosity (OR=2.00, 95% CI: 1.17-3.42) for the Gln399 allele increased the risk of schizophrenia. There was a significant linear trend in risk associated with zero, one, and two 399Gln alleles. The present finding indicates that XRCC1 is a candidate gene for susceptibility to schizophrenia.