One of the Difficulties in Molecular Simulation of Pressure-Driven Fluid Flow in Nanochannels is to Find an Appropriate Pressure Control Method. When Periodic Boundary Conditions (PBCs) Are Applied, a Gravity-Like Field Has Been Widely Used to Replace Actual Pressure Gradients. the Gravity-Fed Method is Not Only Artificial, But Not Adequate for Studying Properties of Fluid Systems Which Are Essentially Inhomogeneous in the Flow Direction. in This Paper, a Method is Proposed Which Can Generate Any Desired Pressure Difference to Drive the Fluid Flow by Attaching a "Pump" to the Nanofluidic System, While the Model is Still Compatible with PBCs. the Molecular Dynamics Model based on the Proposed Method is Applied to Incompressible Flows in Smooth Nanochannels, and the Predicted Velocity Profiles Are Identical to Those by the Gravity-Fed Method, as Expected. for Compressible Flows, the Proposed Model Successfully Predicts the Changes of Fluid Density and Velocity Profile in the Flow Direction, While the Gravity-Fed Method Can Only Predict Constant Fluid Properties. for Fluid Flows in Nanochannels with a Variable Cross-Sectional Area, the Proposed Model Predicts Higher Mass Flow Rates as Compared to the Gravity-Fed Method and Possible Reasons for the Difference Are Discussed. © Springer-Verlag 2012.