Abstract Background Anemia is common among end-stage renal disease (ESRD) patients who undergone hemodialysis. The total reduction of red blood cell (RBC) count is associated with poor prognosis in these patients. Although erythropoietin (EPO) has been used as an effective treatment for ESRD patients with anemia, a large number of patients still present poor responses to EPO treatment. Methods We measured T-cell receptor sequencing profiles, including length of complementarity-deteremining region 3 (CDR3), intra- and inter-group (EPO resistant vs. responsive) clonotype diversity, V(D)J usage profiles and V-J combinations from ESRD patients and to investigate the correlation between these features and EPO treatment efficacy. Results Our results revealed statistical significance in the top 3 ~ 15 most abundant joint distributions of Vβ/Jβ among the two groups, suggesting the importance of V or J gene utilization in the EPO response of ESRD patients. Conclusions In summary, we provided evidence addressing the potential correlation between the immune repertoire and EPO response in ESRD patients. Trial registration TMU-JIRB 201309026. Registered 16 October 2013.