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Background: Recently, despite the steady decline in the tuberculosis (TB) epidemic globally, school TB outbreaks have been frequently reported in China. This study aimed to quantify the transmissibility of Mycobacterium tuberculosis (MTB) among students and non-students using a mathematical model to determine characteristics of TB transmission. Methods: We constructed a dataset of reported TB cases from four regions (Jilin Province, Xiamen City, Chuxiong Prefecture, and Wuhan City) in China from 2005 to 2019. We classified the population and the reported cases under student and non-student groups, and developed two mathematical models [nonseasonal model (Model A) and seasonal model (Model B)] based on the natural history and transmission features of TB. The effective reproduction number (Reff) of TB between groups were calculated using the collected data. Results: During the study period, data on 456,423 TB cases were collected from four regions: students accounted for 6.1% of cases. The goodness-of-fit analysis showed that Model A had a better fitting effect (P < 0.001). The average Reff of TB estimated from Model A was 1.68 [interquartile range (IQR): 1.20–1.96] in Chuxiong Prefecture, 1.67 (IQR: 1.40–1.93) in Xiamen City, 1.75 (IQR: 1.37–2.02) in Jilin Province, and 1.79 (IQR: 1.56–2.02) in Wuhan City. The average Reff of TB in the non-student population was 23.30 times (1.65/0.07) higher than that in the student population. Conclusions: The transmissibility of MTB remains high in the non-student population of the areas studied, which is still dominant in the spread of TB. TB transmissibility from the non-student-to-student-population had a strong influence on students. Specific interventions, such as TB screening, should be applied rigorously to control and to prevent TB transmission among students. [ABSTRACT FROM AUTHOR]