Background and objectiveSmoking is a leading cause of death in the world. Aberrant brain function has been repeatedly linked to tobacco smoking. However, little is known about insula-based resting-state functional connectivity (rsFC) in non-deprived tobacco-dependent smokers. This study characterized the correlation between insula-based rsFC and tobacco dependence severity in non-deprived smokers. MethodsA total of 37 male smokers and 37 age-matched male non-smokers completed resting-state functional MRI (fMRI) scans. The insula-based rsFC differences between smokers and controls were investigated and the correlation between insula-based rsFC and FTND (Fagerstrom Test for Nicotine Dependence) scores were then assessed. ResultsCompared with controls, smokers showed significantly lower rsFC between orbitofrontal cortex, superior frontal gyrus, temporal lobe and insula. The rsFC between orbitofrontal cortex, temporal lobe, inferior parietal cortex, occipital lobe and insula was positively correlated with FTND. However, the rsFC between anterior cingulate cortex and insula was negatively correlated with FTND. ConclusionOur findings suggest differences in brain functional connectivity between smokers and non-smokers. This study sheds new insights into the neural mechanisms of tobacco dependence. In this study, 37 male smokers and 37 age-matched male non-smokers completed resting-state functional MRI (fMRI) scans. These findings provide new insights into the neural mechanisms of tobacco dependence.