〔Abstract〕 Objective To explore the expression and its efficacy in predicting neoadjuvant chemoradiation therapy sensitivityof human antigen R(HuR) in rectal cancer. Methods Fifty-six paired middle-low rectal cancer samples and clinicopathologic characteristics were analyzed. HuR expression in middle-low rectal cancer tissuesand exploratory biopsies was detected by quantitative real-time PCR and immunochemistry. The capability of HuR to influence DNA DSBs inthe presence of chemo-radiation was determined by using comet assay. Results HuR was mostly up-regulated in middle-low rectal cancer tissues and over expression HuR was significantly associated with invasive clinicopathologic characteristics such as advanced TNM stage, positive lymph node invasion and vascular infiltration. The Kaplan-Meier plot of overall survival from TCGA database demonstrated that high HuR expression patient subgroup had a shorter median survival period compared with the low HuR expression subgroup. Moreover, patients with high HuR expression were of inferior therapeutic sensitivity to chemo-radiation therapy. Conclusion HuR is over expressed in rectal cancer and possessed the capabilities to resist chemo-radiation therapy. In addition, inhibition of HuR can improve chemo-radiationtherapeutic response.