Gear flank twist has a significant effect on the load-carrying capacity. However, most prediction models of gear flank twist can’t be applicable for gears with profile modification. A new method for predicting gear flank twist for the generating grinding process is developed in this paper, taking into consideration the effect of lead modifications, profile modifications and position errors of CNC machine tools on gear flank twist. And the influences of four gear parameters on gear flank twist were studied using orthogonal experiments, which proves that the change of module has the greatest effect on gear flank twist. And the maximal profile modification value has minimal effect on gear flank twist. The experimental results proved that the model can accurately predict the gear flank twist. Besides, this paper described an gear parameters optimization study to reduce gear flank twist based on nine well-planned orthogonal experiments.