An apparatus for controlling driving a vehicle based on driver's fatigue includes a first information collector to collect biological information of a driver, a second information collector collect road condition information, a route calculator configured to calculate a desired route from a current position of the vehicle to a destination, a fatigue index calculator to divide a route, and to calculate a fatigue index for each section, a predicted fatigue index calculator to calculate a predicted fatigue index corresponding to the desired route, and a function provider configured to calculate a compensation value according to the predicted fatigue index, and to calculate a final operation value.