Recent studies have documented declined global cognitive function and abnormal task-related brain activation in chronic cigarette smokers. However, the effects of long-term heavy smoking on task-independent baseline brain activity are still unknown. Here, we used a regional homogeneity (ReHo) method combined with functional magnetic resonance imaging (fMRI) to investigate spontaneous neural activity in the resting state in heavy smokers. Compared with controls, heavy smokers exhibited decreased ReHo in prefrontal regions, as well as increased ReHo in insula and posterior cingulate cortex. Our study may better our understanding of the neurobiological consequences of smoking.