Background Few studies have been previously published about the resting state brain activity in young chronic smokers, although many previous fMRI studies have shown that the task-related activity pattern is altered in chronic smokers. Methods In the present study, forty-five healthy smokers (age: 27.9 ± 5.6 year) and forty-four healthy non-smoking control subjects (age: 26.3 ± 5.8 year) have been imaged with functional magnetic resonance imaging (fMRI) and analyzed with the regional homogeneity (ReHo) approach. Results Compared with healthy controls, decreased ReHo was found in smokers in the right inferior frontal cortex and increased ReHo was found in the left superior parietal lobe (P < 0.01, 35 Voxels,Alphasim corrected). Conclusions Our data suggested that, during resting state, neural function is less synchronized in the right inferior frontal cortex and more synchronized in the left superior parietal lobe in chronic smokers compared to non-smokers. The decreased synchronization in the right inferior frontal cortex may reflect lacking of control over reward-related behavior, and the increased synchronization may reflect smoking urges.