Abstract: Testing the fatigue state of high-speed railway drivers before driving can prevent fatigue driving and ensure driving safety. Therefore, this article designed and developed pre-driving fatigue detection system for high-speed railway drivers. In this study, the heart rate variability, flash fusion frequency, blood oxygen, blood pressure, breathing, body temperature and other psychological and physiological indicators of high-speed railway drivers were examined, subjective fatigue and sleep time the night before departure were investigated, and 180 valid data were obtained. The factor analysis was carried out using statistical product and service solution software. The comprehensive fatigue index was calculated by factor analysis with statistical product and service solution software, and the fitness of the integrated fatigue detection model was verified. By K-means clustering analysis and CART decision tree algorithm, the fatigue index was categorized into 4 levels. The pre-driving fatigue detection system for high-speed railway drivers can complete all the tests within 5 minutes and report immediately, which can prevent high-speed railway drivers from driving fatigued and urge them to take a rest before leaving. The system additionally provides massage relaxation operation and health knowledge push, while establishing personal files for long-term monitoring of driver fatigue.