The present invention discloses a driver's fatigue detection system and method. The system comprises a vital sign detection device generating at least one personal vital sign value； a storage device storing a linear statistic equation； a processor electrically connected with the vital sign detection device and the storage device； and a display device electrically connected with the processor. The processor receives the personal vital sign value, retrieves the linear statistic equation, substitutes the personal vital sign value into the linear statistic equation to generate a predictive vehicle deviation value, and determines whether the predictive vehicle deviation value is over a preset vehicle deviation value. If yes, the processor generates an alert signal to the display device to present an alert image. The present invention determines whether the stability of the driver is decreasing according to his physiological status and reminds the driver to avoid a traffic accident beforehand.
