Energy management strategies (EMSs) are critical for the improvement of fuel economy of plug-in hybrid electric vehicles (PHEVs). However, conventional EMSs hardly consider the influence of uphill terrain on the fuel economy and battery life, leaving vehicles with insufficient battery power for continuous uphill terrains. Hence, in this study, an optimal control strategy for a PHEV based on the road grade information is proposed. The target state of charge (SOC) is estimated based on the road grade information as well as the predicted driving cycle on uphill road obtained from the GPS/GIS system. Furthermore, the trajectory of the SOC is preplanned to ensure sufficient electricity for the uphill terrain in the charge depleting (CD) and charge sustaining (CS) modes. The genetic algorithm is applied to optimize the parameters of the control strategy to maintain the SOC of battery in the CD mode. The pre-charge mode is designed to charge the battery in the CS mode from a reasonable distance before the uphill terrain. Finally, the simulation model of the powertrain system for the PHEV is established using MATLAB/Simulink platform. The results show that the proposed control strategy based on road-grade information helps successfully achieve better fuel economy and longer battery life.