In a control system for an internal combustion engine having a plurality of cylinders and mounted on a vehicle, in which the engine operation is switched based on the throttle opening between a full-cylinder operation in which all of the cylinders are operative and a cut-off cylinder operation in which some of the cylinders are inoperative, and a running control including a cruise control in which the vehicle runs at a desired vehicle velocity and a preceding vehicle follow-up control in which the vehicle runs at a desired vehicle velocity to maintain a desired inter-vehicle distance from a preceding vehicle are conducted. In the system, an acceleration suppression control is conducted if the engine operation is switched from the cut-off cylinder operation to the full-cylinder operation when the running control is in progress. With this, sharp or drastic acceleration accompanying torque fluctuation is effectively avoided, when the engine operation is switched to the full-cylinder operation.