PurposeIn addition to its toxic effects on the human cardiovascular and respiratory systems, tobacco dependence also causes damage to brain function and cognitive activity. Therefore, the main objective of this study was to investigate the effects of acute aerobic exercise on food-reward function and its food-cued prefrontal brain activation in tobacco-dependent individuals. MethodNinety-three participants who met the study criteria were randomly divided into a moderate-intensity exercise group (65%-75% HRmax), a high-intensity exercise group (75%-85% HRmax), and a quiet control group (n = 31 in each group). Participants were asked to perform a 35-minute target-intensity exercise or rest. The participants took the Leeds Food Preference Questionnaire and the Visual Food Cues Paradigm Task immediately before the experiment and immediately after completing the exercise or control intervention, and oxyhemoglobin concentrations in each prefrontal brain region were measured at the same time as the Visual Food Cues Paradigm Task. ResultsAcute aerobic exercise significantly increased implicit cravings for low-calorie sweets in nicotine-dependent individuals (high: p = 0.040; moderate: p = 0.001), while acute moderate-intensity aerobic exercise also significantly increased the activation levels of the left dorsolateral prefrontal cortex (DLPFC: CH15: p = 0.030; CH22: p = 0.003) as well as the left orbitofrontal area (OFC: CH21: p = 0.007) in the food-reward brain region in nicotine-dependent individuals. ConclusionAcute aerobic exercise improves food-reward function and effectively increases activation levels in the DLPFC and OFC cerebral cortex in tobacco-dependent individuals, facilitating restoration of sensitivity to their drug-hijacked natural reward circuits.