Purpose This study aimed to investigate the relationship between health information literacy and quality of life and to explore the mediating role of self-management in this relationship among COPD patients in Hunan, China. Methods Following the STROBE guidelines, this cross-sectional study employed convenience sampling to recruit 432 COPD patients from six tertiary hospitals in Hunan Province, China, between December 2022 and August 2023. Data collection instruments included the Health Literacy Self-Assessment Questionnaire (HLSQ), the COPD Self-Management Scale, and the COPD Assessment Test (CAT). Descriptive statistics were used to summarize participants' characteristics. Pearson correlation analysis and SPSS 26.0's macro program for mediation analysis were used, with a significance level set at p < 0.05. Results Health information literacy showed a strong positive correlation with both self-management (r = 0.742, p < 0.001) and quality of life (r = -0.748, p < 0.001). Additionally, self-management was positively associated with quality of life (r = -0.861, p < 0.001). Self-management significantly mediated the relationship between health information literacy and quality of life, accounting for 67.4% of the total effect. Conclusions The mediating effect of self-management on the relationship between health information literacy and quality of life in COPD patients is established. Measures are needed to improve health information literacy, enhance self-management, and improve health outcomes.