Background End-stage renal disease (ESRD) patients undergoing hemodialysis have to face many symptoms from disease progression and treatment. These symptoms cause suffering and affect physical, psychological, emotional, social, and spiritual of the patients, resulting in decreased quality of life and might increase the death rate of these patients. Therefore, the study of symptoms in ESRD patients undergoing hemodialysis will lead to effective symptom management and maximize benefits for the patients. The purpose of this study was to explore the symptom clusters of ESRD patients undergoing hemodialysis. Materials and Methods The sample of this descriptive study consisted of 150 ESRD patients undergoing hemodialysis from two dialysis centre of the university hospital and specialized kidney hospital in Bangkok. The instruments consisted of Personal Information Questionnaire (PIQ) and Dialysis Symptom Index-THAI (DSI-THAI). The data were analyzed by exploratory factor analysis. Results The 8 clusters of symptoms were found: 1) gastrointestinal, 2) musculoskeletal and fluid volume 3) neurological 4) irritation of the mucous membranes and skin 5) depression 6) sleep disturbance 7) sexual 8) anemic. Conclusion The results of this study can be raised awareness and used as the information for the health-care provider to develop the intervention to manage unpleasant symptoms which lead to improving the quality of life.