A method of predicting and controlling NOx generation amount is provided. The method includes calculating a difference between an actual and a reference NOx exhaust amount and analyzing influence of the in-cylinder pressure at a combustion start time, an oxygen amount in EGR gas, and a fuel injection timing. A NOx rate of change is calculated based on change in the in-cylinder pressure at the combustion start time, the oxygen amount in the EGR gas, and the fuel injection timing. A variation width and a NOx value are calculated at the combustion start time, the oxygen amount in the EGR gas, and the fuel injection timing. The NOx value is adjusted based on the NOx value adjustment amount and a NOx final value is determined. A target boost pressure, a target oxygen amount, and a target fuel injection timing are determined to provide a final command signal.