<p>Mental and substance use disorders profoundly affect global population health, while there is a notable absence of systematic studies focusing on their burden in the Chinese population. We estimated the burden of Global Burden of Diseases (GBD) 2021 for 10 mental disorders and two types of substance use disorders in China from 1990 to 2021. We presented the numbers and rates of prevalence, disability-adjusted life years (DALYs), years of life lost (YLL) and years lived with disability (YLDs), from national and 33 province-level administrative units in China. In 2021, China contributed 174.4 million prevalent cases (95% uncertainty interval [UI] 162.4-188.4 million) of mental disorders and 27.0 million prevalent cases (23.8-30.7 million) of substance use disorders. The age-standardized DALY rate for mental and substance disorders in China was lower than that in countries with high Socio-demographic Index (SDI) and middle SDI, as well as lower than global level. Depressive disorder and anxiety disorder being the two leading causes, accounting for 61.1% of mental disorder YLDs, and were most prevalent among individuals aged 15 and over. Population growth was an important contributor to the 62.0% increases in DALYs for mental disorder. Regionally, the age-standardized prevalence rates for mental disorders were higher in Eastern China, while substance use disorders were more prevalent in Western regions. These findings showed the burden of mental disorders in China has increased mainly due to the population growth and population aging. The comprehensive prevention and early intervention strategies is urgent to mitigate the burden and the impact for the public.</p>