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 at least a cruise control in which the vehicle runs at a desired vehicle velocity is conducted, the engine operation is switched to the full-cylinder operation when it is determined that deceleration is required in the running control, so as to increase pumping loss (engine loss). With this, it becomes possible to generate the deceleration sufficiently as desired, when, for example, the vehicle descends a downhill.