Titanium alloys are being widely used in the aerospace, biomedical and automotive industries because of their good strength-to-weight ratio and superior corrosion resistance. Surface roughness is one of the most important requirements in machining of Titanium alloys. This paper describes mathematically the effect of cutting parameters on Surface roughness in end milling of Ti6Al4V. The mathematical model for the surface roughness has been developed in terms of cutting speed, feed rate, and axial depth of cut using design of experiments and the response surface methodology (RSM). Central composite design was employed in developing the surface roughness models in relation to primary cutting parameters. The experimental results indicate that the proposed mathematical models suggested could adequately describe the performance indicators within the limits of the factors that are being investigated. The developed RSM is coupled as a fitness function with genetic algorithm to predict the optimum cutting conditions leading to the least surface roughness value. MATLAB 7.0 toolbox for GA is used to develop GA program. The predicted results are in good agreement with the experimental one and hence the model can be efficiently used to achieve the minimum surface roughness value.