Background <p>This study aimed to examine the association between health literacy and illness perception among Chinese patients with chronic disease in the community through a national cross-sectional study.</p> Methods <p>This cross-sectional study was conducted in China from June 20, 2022, to August 31, 2022, and used a multistage sampling approach to select patients with chronic diseases. The study included 5,525 participants from 15 provinces, drawn from the Psychology and Behavior Investigation of Chinese Residents in 2022. We constructed univariate analysis, smooth curve fitting, threshold saturation effect analysis, and forest plot of subgroup analysis to evaluate the association between health literacy and illness perception.</p> Results <p>The analysis revealed an inverted J-shaped association between health literacy and illness perception (<i>P</i> &lt; 0.001). Moreover, the identified inflection point was 22.22. When the health literacy score was below 22.22, illness perception exhibited a positive association with health literacy (β = 0.12, 95%CI = 0.03, 0.21, <i>P</i> = 0.009). When the health literacy score was higher than 22.22, illness perception decreased with the increasing health literacy (β=-0.23, 95%CI=-0.27, -0.19, <i>P</i> &lt; 0.001). The significant association between health literacy and illness perception did not differ significantly across subgroups, except for the Hukou subgroup.</p> Conclusions <p>This study determined a threshold of health literacy that was associated with the illness perception of Chinese chronic disease patients. Additionally, an inverted J-shaped association between health literacy and illness perception was observed, suggesting that targeted health literacy intervention measures should be tailored to specific chronic disease groups rather than a uniform approach.</p> Clinical trial number <p>Not applicable.</p>