After irradiation results in cytotoxic effects by DNA damage, base excision repair (BER) pathway is involved in the repair of single-strand breaks and nonhomologous end joining and homologous repair of double-strand breaks caused by radiotherapy. Alterations in the function of BER DNA repair genes may affect DNA repair proficiency and influence the response of patients with cancer to radiotherapy. The association of single nucleotide polymorphisms of BER DNA repair X-ray repair cross-complementing group 1 protein (XRCC1) and risk of radiotherapy-induced ≥grade 2 acute skin reaction in patients with breast cancer was examined. It was found that the risk of ≥grade 2 acute skin toxicity after radiotherapy could be increased by 2.86-fold in patients carrying the XRCC1 -77TC and CC genotypes (p = 0.016). However, the other three coding XRCC1 variants did not influence the risk of ≥grade 2 acute skin toxicity for patients with breast cancer after radiotherapy. Our results suggested that the XRCC1 polymorphism is associated with increased risk of radiation-induced acute skin reaction in a Chinese population.