In recent years, storage of carbon dioxide (CO2) in saline aquifers has gained intensive research interest. The implementation, however, requires further research studies to ensure it is safe and secure operation. The primary objective is to secure the CO2 which relies on a leak-proof formation. Reservoir pressure is a key aspect for assessment of the cap rock integrity. This work presents a new pressure control methodology based on a nonlinear model predictive control (NMPC) scheme to diminishing risk of carbon dioxide (CO2) back leakage to the atmosphere due to a fail in the integrity of the formation cap rock. The CO2 sequestration process in saline aquifers is simulated using ECLIPSE-100 as black oil reservoir simulator while the proposed control scheme is realized in MATLAB software package to prevent over-pressurization. A modified form of growing and pruning radial basis function (MGAP-RBF) neural network model is identified online for prediction of reservoir pressure behaviors. MGAP-RBF is recursively trained via extended Kalman filter (EKF) and unscented Kalman filter (UKF) algorithms. A set of miscellaneous test scenarios has been conducted using an interface program to exchange ECLIPSE and MATLAB in order to demonstrate the capabilities of the proposed methodology in guiding saline aquifer to follow some desired time-dependent pressure profiles during the CO2 injection process.