Abstract: The purpose of this study was to explore the effects of mental fatigue on cognitive control and the regulation effects of reward on cognitive control under mental fatigue. In Experiment 1, the effects of mental fatigue on proactive control and reactive control were investigated by combining the mental fatigue time on task paradigm (TOT) with AX-continuous performance task (AXCPT) . The results showed that the task performance was improved in AY sequence but decreased in BX sequence under mental fatigue. In Experiment 2, the moderating effect of reward on cognitive control under mental fatigue was investigated by using a reward version of AX-CPT task. The results showed the subjects' performance of AY sequence tasks was improved and the performance tendency of BX sequence tasks was decreased when the reward was not available. However, the subjects' performance of AY sequence tasks was weakened and the performance of BX sequence tasks was promoted when the reward was provided. The conclusions of this study were: 1) Mental fatigue has different effects on the two forms of cognitive control, the proactive control was weakened and the reactive control was enhanced under mental fatigue; 2) Reward plays a moderating role in individual's cognitive control under mental fatigue. The proactive control was weakened and the reactive control was enhanced without reward; however, the proactive control was enhanced and the reactive control was weakened with reward.