In a retrospective study design, we explored the relationship between serum thymidine ki-8 nase 1 (TK1) concentration before radiotherapy and clinical parameters and evaluated the prognostic value of serum TK1 concentration before radiotherapy in breast cancer patients with type 2 diabetes mellitus. The present study finally consisted of 428 breast cancer patients with a mean age of 53.0 years. Compared with low TK1 group, the high TK1 group tended to have larger tumor size (P=0.011) and had more lymph node number (P=0.021). Significant differences were also observed in clinical stages I, II and III (P=0.000). There was no significant difference between TK1 and other clinical parameters. For disease-free survival (DFS), the univariate analysis indicated that the high TK1 increased the risk of poor prognosis (HR = 2.38, 95% CI: 1.64-4.23, P=0.000). The Kaplan-Meier curve indicated the high TK1 group was poorer than that in the low TK1 group (P = 0 . 0 02) . For the overall survival (OS), similar results were found that the high TK1 was related to poor OS (HR = 1.89, 95% CI: 1.34-3.67, P=0.000). The multivariate Cox regression indicated that the TK1 was still associated with DFS (HR = 1.83, 95% CI: 1.22-3.17, P=0.001) and OS (HR = 1.63, 95% CI: 1.19-2.08, P=0.006). The high pretreatment serum TK1 levels in breast cancer patients were associated with poor OS and DES. TK1 could be a potential predictive factor in differential diagnosis of poor prognosis from all patients.