XRCC1 polymorphisms may alter the individual’s capacity to repair DNA damages and may increase the risk for developing different types of cancer, including Non-Hodgkin Lymphoma (NHL). The purpose of our study was to investigate the association between XRCC1 Arg194Trp and Arg399Gln polymorphisms and risk of NHL, in a case-control study consisted of 81 patients with NHL and 113 healthy controls. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods were performed to determine the XRCC1 genotypes. A statistically significant association was observed between the XRCC1 Arg194Trp polymorphism and risk of NHL (p < 0.0001, OR = 7.01, 95% CI = 2.488-19.753) in both male and female. We found no association between NHL and control groups with respect to XRCC1 Arg399Gln polymorphism (p = 0.4867, OR = 1.346, 95% CI = 0.5822-3.111). Also, we did not find differences between the XRCC1 polymorphisms and NHL risk taking into account the IPI score, ECOG performance status, Ann Arbor stage and the treatment outcome (p > 0.05, for all comparisons). Our results suggested an increased risk for NHL regarding the XRCC1 Arg194Trp polymorphism in a Romania population, while XRCC1 Arg399Gln polymorphism is not associated with NHL. Further work is needed to validate these results on a larger sample study.