The combustion process in Homogeneous Charge Compression Ignition (HCCI) is mainly controlled by the chemical kinetics reactions of the fuel-air mixture. So, the HCCI combustion process is sensitive to the charge temperature, pressure, and the mixture composition during the compression stroke. In the present work, the simulations results of the HCCI combustion are performed using a single zone model with detailed kinetic reaction mechanism. The simulation study is achieved to predict the auto-ignition timing and the combustion characteristics of the HCCI engine fueled with blends of ethanol and diesel at different volume percentage. The premixed ratio of the ethanol–diesel fuel blends is used in this study to control the auto-ignition timing and the combustion characteristics at a wide range of the engine load. The main pathway of this work is to study the influence of engine operating parameters which including the premixed ratio, fuel-air equivalence ratio on the combustion characteristics of HCCI engine. These effects are studied and traced through the simulation result data of the in-cylinder pressure, temperature, and heat release at different premixed ratios of ethanol-diesel fuels blends of 0, 10, 20, 30,40 and 50% (by volume). The engine speed is kept constant at 1500 RPM. The obtained results show that the increase of the premixed ratio of ethanol in diesel fuel blends in the range up to 50% will decrease the peak cylinder pressure and temperature and decrease the combustion duration.