First, a 2D orthogonal cutting model for titanium alloy is constructed by finite element method in this study. The cutting tool is incrementally advanced forward from an incipient stage of tool-workpiece engagement to a steady state of chip formation. Cockroft and Latham fracture criterion  is adopted as a chip separation criterion. By changing the settings of cutting variables such as cutting speed, depth of cut and tool rake angle to investigate the chip formation process and the variation of cutting performance during titanium cutting simulation. The changes of chip type, cutting force, effective stress/strain and cutting temperature with different cutting condition combinations are thus analyzed. The result demonstrates that the serrated chip type is obviously produced when cutting titanium alloy. Next, water-based and oil-based cutting fluids are employed in conjunction with proper cutting parameter arrangements to perform up-milling experiments. By measuring the cutting force, surface roughness and tool wear to investigate the effect of these combinations of milling variables on the variation of cutting performance for Ti-6Al-4V. The chip shape and cutting force obtained from the experiment are compared with those calculated from simulation. It is shown that there is a good agreement between simulation and experimental results.