Objective:To investigate the differences of resting-state spontaneous neural activity between smoking addicted teenagers and healthy non-smokers.Methods:In the current study, the percent amplitude of fluctuation (perAF) approach was applied to explore the differences of resting-state spontaneous neural activity between smoking addicted teenagers and healthy non-smokers.Pearson correlation analysis was used to investigate the relationships between the altered perAF values and smoking years, fagerstrom test for nicotine dependence (FTND) and pack-years of smokers.Results:Compared with healthy non-smokers, smoking addicted teenagers showed increased perAF values in the parahippocampal gyrus (smoking addicted teenagers: 2.026 5±0.516 7, nonsmokers: 0.781 6±0.148 9), middle temporal gyrus (smoking addicted teenagers: 0.796 7±0.203 2, nonsmokers: 0.545 5±0.134 1), and superior frontal gyrus (smoking addicted teenagers: 2.734 5±0.372 8, nonsmokers: 1.962 4±0.416 8) (all P<0.001). It was noteworthy that the perAF values of the parahippocampal gyrus were negatively correlated with smoking years of smoking addicted teenagers( r=-0.6007, P=0.0084). Conclusion:Compared with healthy non-smokers, the resting-state regional neural activity in smoking addicted teenagers was altered, mainly manifested as increased perAF value in the parahippocampal gyrus, which is correlated with smoking years of smoking addicted teenagers.These findings may help us understanding neural mechanisms underlying nicotine addiction of smoking addicted teenagers.