Introduction: The potential association between cognitive functions, mood states, and their effect on driving behavior is complex and has been previously studied in most cases suggesting mood and emotion as possible factors in high-risk driving behaviors. However, their outcome measures are subjective and prone to biases. In this study, we add objective physiological data to explore the physiological and behavioral background of the relevance of mood in high risk driving by functional magnetic resonance imaging (fMRI). Methods: In this study, 28 male right-handed drivers, aged between 20 to 30 years will be randomly selected from records of drivers in the central traffic department and included in the study. Each participant will drive virtually in an fMRI-compatible driving simulator, after positive, negative, and neutral mood induction, and fMRI will be performed to explore driving-related brain activity alterations and the impact of mood state on these effects. All data analyses will be performed using MATLAB (MathWorks, Natick, MA) and the Statistical Parametric Mapping (SPM12) software package. Results: This protocol study introduced a novel protocol to induce positive, negative, and neutral moods and study the impact of mood on driving. Conclusion: Comparing brain activity during driving after positive, negative, and neutral mood induction, this study will help to understand effects of different mood states on driving behavior. Furthermore, comparing the fMRI images of driving under different mood states will clarify the physiological foundation of the impact of mood states on driving behavior. The results of this study will help to introduce physiologically informed preventive or reinforcement strategies to control mood states while driving, and therefore might help to reduce a significant proportion of preventable car accidents.