Objectives: To explore the mediating effect of self-efficacy (SE) on the relationship between medication adherence (MA) and illness perception (IP) in patients with rheumatoid arthritis (RA). Methods: A convenient sampling method was used to select 238 RA patients undergoing treatment at two hospitals in Guangzhou, China. A cross-sectional survey was conducted, utilizing a general information questionnaire, a chronic disease SE scale, an IP scale, and the Medication Adherence Rating Scale (MARS-A). R software (Version 4.2.2) was used to construct a mediation model to examine the impact of SE and IP on MA among RA patients. The bootstrap method was employed to validate the mediating role of SE. Results: The average scores for IP, SE, and MA were 120.50±12.32, 29.36±8.49, and 21.22±2.96, respectively. Pearson correlation analysis revealed that SE was positively correlated with IP (r=0.23, p<0.01) and MA (r=0.195, p<0.001). IP was also positively correlated with MA (r=0.532, p<0.05). The mediating effect of SE in the relationship between IP and MA was confirmed. Conclusion: SE partially mediates the relationship between IP and MA in patients with RA.