The invention discloses a safe intelligent driving method and system. The method comprises the following steps: obtaining a human body comprehensive fatigue index I by a fatigue analysis and vehicle control system through monitoring results, monitored by a fatigue sensing system, of physiological indexes of a human body; predicting whether a vehicle is in a safety region or not according to vehicle state data of a vehicle state database, perception data of a roadside sensor and a vehicle sensor of a sensor perception database, and vehicle driving route data of a geographic information database; and judging and selecting driving modes according to driving time, the human body comprehensive fatigue index I and whether the vehicle is in the safety region or not, and sending a control instruction to an automatic driving system according to judging results. The safe intelligent driving method and system disclosed by the invention have the beneficial effects that the influences of the driving time, human body comprehensive fatigue conditions and whether the vehicle is in the safety region or not on vehicle driving safety are comprehensively taken into account; a more appropriate drivingmode is intelligently selected; the vehicle driving safety is greatly improved, and the driving pressure of a driver is relieved.