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Background This study aimed to analyze the relationship between health literacy and quality of life in patients with TB in Tibet and explore the mediating effects of self-efficacy and self-management in the relationship between health literacy and quality of life. Methods We used a convenience sampling method to select 271 cases of patients with TB in Tibet to conduct a survey of their general information, health literacy, self-management, self-efficacy and quality of life, and to construct structural equation models. Results The total health literacy score of patients with TB in Tibet was 84.28±18.57, while the lowest score was for information acquisition ability (55.99±25.66). Scores for quality of life were generally lower than the norm (patients with chronic diseases from other cities in China) (p<0.01). Moreover, self-efficacy and self-management mediated the relationship between health literacy and quality of life (p<0.05). Conclusions In Tibet, patients with TB have a low level of health literacy and an average level of quality of life. Emphasis should be placed on improving information access literacy, role-physicals and role-emotional to improve overall quality of life. The mediating roles of self-efficacy and self-management between health literacy and quality of life may provide a basis for further interventions. [ABSTRACT FROM AUTHOR]