ObjectiveTo analyze the prevalence, regional differences, and influencing factors of depression in the middle-aged and elderly population aged 45 years and above in China. MethodsData were obtained from the latest survey data of the China Health and Retirement Longitudinal Study (CHARLS) in 2020, and the CES-D-10 scale was used to assess depression among respondents, and χ2 test and binary logistic regression were used to screen for the influencing factors of depression. ResultsA total of 10 583 valid samples were included, with 47.7% males and 52.3% females, and the mean age was (65.3±8.0) years. The average CES-D-10 scale score of the study population was (9.11±6.53), and the prevalence rate of depression was 40.5% (95%CI 39.6% to 41.5%), with a significantly higher prevalence rate of depression in the Midwestern population than the Eastern population. The gender, age, living with a partner, education, region, urban/rural, duration of sleep, internet access, alcohol consumption, number of chronic diseases, and the presence of ADL and IADL disorders are the influencing factors of depression in middle-aged and elderly populations. ConclusionThe prevalence of depression in the middle-aged and elderly population in China is high, but there are significant differences in the prevalence rates of populations with different characteristics, and the high-risk groups should be emphasized when improving the mental health of the middle-aged and elderly population.