The DNA repair gene X-ray cross-complementing group 4 (XRCC4), a member of the non-homologous end-joining (NHEJ) repair system, plays a major role in the repair of the double-strand breaks of the DNA sequence. This gene is critical to the maintenance of overall genome stability, and is also thought to play a key role in human carcinogenesis. In this case-control study, several novel polymorphic variants of XRCC4, including C-1622T (rs7727691), G-1394T (rs6869366), C-571T (rs2075686) and intron3 DIP (rs28360071), were investigated, and the correlation of these variants to prostate cancer susceptibility in a Taiwanese population was observed. A total of 134 prostate cancer patients were recruited along with 134 age-matched healthy controls, and the association of their selected genotypes with susceptibility to prostate cancer was determined. The G-1394T variant of XRCC4 proved, after analysis of the frequencies of each variant in the prostate cancer and control groups, to be a significant single nucleotide polymorphism (SNP) in prostate carcinogenesis. Our data clearly indicate that the heterogeneous G of G-1394T increases the risk of suceptibility to prostate cancer (P=0.0106), while no difference in distribution of XRCC4 C-1622T (rs7727691), C-571T (rs2075686) or intron3 DIP (rs28360071) between the prostate cancer and control groups was found. In conclusion, our findings suggest that the G allele of XRCC4 G-1394T may be responsible for prostate carcinogenesis, and could be useful in the early detection and prevention of the disease.