Laser cutting of medium density fibreboard (MDF) is a complicated process and the selection of the process parameters combinations is essential to get the highest quality of the cut section. This paper presents laser cutting of MDF based on design of experiments (DOE). CO2 laser was used to cut three thicknesses 4, 6 and 9 mm of MDF panels. The process factors investigated are: laser power, cutting speed, air pressure and focal point position. In this work, cutting quality was evaluated by measuring, upper kerf width, lower kerf width, ratio between the upper kerf width to the lower kerf width, cut section roughness and the operating cost. The effect of each factor on the quality measures was determined and special graphs were drawn for this purpose. The optimal cutting combinations were presented in favours of high quality process output and in favours of low cutting cost.