Abstract: To investigate the influences of circumference on the releases of volatile components in mainstream cigarette smoke, 307 volatile and semi-volatile components in mainstream smoke of king-sized (CZ), demi-slim (ZZ) and slim (XZ) cigarette samples were analyzed by GC-MS. Combined with multivariate statistical analysis method in omics, the differences in volatile compound releases in mainstream smoke of the cigarettes with different circumferences were systematically studied. The results showed that: 1) Divided by functional groups, the releases of volatile components such as phenols, aldehydes, ketones and acids groups were higher, followed by hydrocarbons, alcohols, lactones and pyridine derivatives groups, and the releases of other volatile components were slightly lower overall. The releases and dispersion degrees of different volatile component groups generally followed the trend of CZ > ZZ > XZ samples, and there were significant differences between CZ and XZ samples. 2) Cigarette samples with different circumferences could be effectively distinguished by the OPLS-DA method. According to variable importance projection value (VIP > 1) and variance analysis (P < 0.05), 35, 12 and 12 characteristic differential compounds were screened out, respectively. Compared with ZZ sample, only down-regulated characteristic differential compounds were found in mainstream smoke of XZ sample. 3) Based on the release per unit tar, 29 differential compounds were screened out, which could be clearly divided into three groups, including 12, 7 and 10 compounds, respectively. Among them, the total release of the first group was higher in the mainstream smoke of the CZ sample, and the total releases of the other two groups were higher in the mainstream smoke of the XZ sample. The correlation between the releases of differential compounds and their correlations with tar were generally consistent, and it showed a certain corresponding trend in the releases of volatile components in mainstream smoke between samples with different circumferences. The differences between the releases of volatile components in mainstream smoke of cigarettes with different circumferences were systematically compared at the molecular level, which could provide technical support for quality improvement and development of cigarette.