Abstract: Objective This study aims to analyze the disease burden and changing trends of tuberculosis(TB) among young and middle-aged populations in China, providing a scientific basis for strengthening TB prevention and control measures in our country. Methods Using the data from GBD 2021, the APC model was employed to assess the changes in TB prevalence and mortality in China between 1990 and 2021, and to analyze the drug resistance of TB. Results Between 1990 and 2021, the number of tuberculosis cases among young and middle-aged populations in China increased annually (EAPC=0.55; 95% CI:0.37 to 0.73). The estimated number of latent tuberculosis infections (LTBI) rose from 220 million in 1990 to 280 million in 2021, while the number of active tuberculosis cases decreased from 826,000 to 426,000 during the same period.Both the prevalence and mortality rates showed a downward trend across all age groups in males and females, but the prevalence increased significantly with age, peaking at 50-54 years. Compared to females, males bore a heavier burden of TB across all age groups. From 1990 to 2021, the most significant contributions to the mortality burden of TB among young and middle-aged populations were extensive drug-resistant tuberculosis (XDR-TB) and multidrugresistant tuberculosis (MDR-TB) without extensive drug resistance, while the prevalence was predominantly LTBI, maintaining a 90% percentage across all age groups. The impact of age on the prevalence and mortality rates of TB showed an approximately linear increase. The age effect demonstrated a declining trend in both the prevalence and mortality rates of TB across all age groups. The cycle effect indicated that the prevalence of TB initially increased and then decreased over time, with the lowest risk observed between 2012 and 2016 (RR=0.91,95% CI:0.89~0.92). The mortality rate of TB showed a significant decline over time, with an average annual reduction exceeding 5% across all age groups. The cohort effect revealed that the later the birth year, the lower the risk of TB, particularly among individuals born after 1972, who exhibited the lowest overall risk. The cohort born between 1997 and 2001 had the lowest risk (RR=0.91,95% CI:0.87~0.95), with similar mortality rates. Conclusions Although the tuberculosis disease burden among China's middle-aged and young population has somewhat eased over the past 30+ years, the rising number of LTBI cases and the persistent severity of MDR-TB-with heavier burdens on middle-aged populations-call for targeted LTBI screening and preventive treatment for high-risk subgroups (e.g., diabetic patients, close contacts, and immunocompromised individuals), as well as systematic intervention and monitoring, to reduce the social burden and economic losses of the disease.