BACKGROUND The tract-based spatial statistics (TBSS) method was used to investigate the changes of white matter microstructure in tobacco addicts, and to analyze its correlation with smoking index, smoking years, and daily smoking amount. MATERIAL AND METHODS Routine magnetic resonance imaging (excluding intracranial lesions) and diffusion tensor imaging (DTI) sequence scanning were performed in 156 nicotine addicts (nicotine dependence group) and 81 non-nicotine addicts (control group) recruited from the study group. TBSS method was used to preprocess DTI data, and age and education level were taken as covariables to statistically analyze relevant parameters between nicotine dependence group and control group, such as fractional anisotropy (FA) value and smoking index. Spearman correlation analysis was performed on smoking status and FA values in brain regions with significant differences between nicotine dependent group and control group, and the test level alpha was 0.05. RESULTS Compared with control group, FA values of white matter in part of the posterior limb of the right inner capsule (r=-0.428, P=0.003), the right superior radiating crown (r=-0.136, P=0.004), the right posterior radiating crown (r=-0.229, P=0.003), the right superior longitudinal bundle (r=-0.474, P=0.002), the right inferior longitudinal bundle (r=-0.354, P=0.003) and the inferior frontal occipital bundle (r=-0.310, P=0.002) were decreased, which were negatively correlated with smoking index (P<0.05). CONCLUSIONS Nicotine can damage the microstructure of white matter in specific brain regions and damage neurons, with cumulative effects.