Abstract: Objective: To explore the mediating role of perceived social support between illness perception and illness acceptance in patients with maintenance hemodialysis (MHD). Methods: A total of 236 hemodialysis patients who were treated in the Blood Purification Department of the First Affiliated Hospital of Guangxi Medical University from August 2022 to February 2023 were selected as the research objects by the convenient sampling method. The patients were investigated with the general data questionnaire, acceptance of illness scale (AIS), brief illness perception questionnaire (BIPQ) and perceived social support scale (PSSS). Results: The MHD patients’disease acceptance score was 19.00 (15.00-26.00), illness perception score was 53.00 (40.00-61.00), and perceived social support score was 48.50 (41.00-60.00); the level of perceived social support was positively correlated with illness acceptance (r＝0.797, P＜0.001), and negatively correlated with illness perception (r＝-0.807, P＜ 0.001) and illness acceptance was negatively with illness perception (r＝-0.917, P＜0.001); there was a partial mediating effect in perceived social support between illness perception and illness acceptance, with a mediating effect of 11.1%. Conclusion: Perceived social support is a mediating variable between illness perception and disease acceptance. Clinical medical workers can improve patients’negative illness perception by improving their perceived social support level, so as to improve their illness acceptance.