The mechanism in drilling carbon fiber reinforced plastic (CFRP) and titanium stack materials differs from that in drilling single material. Titanium chips evacuation through the hole deteriorates the CFRP hole quality. To investigate the quality characteristics of CFRP-layer in drilling of CFRP/Ti stacks, orthogonal experiments are designed for analyzing the effects of both titanium chips and cutting parameters on drilling performance of CFRP-layer. The thrust force, torque and titanium chip morphology are firstly observed. Then the mechanism of hole diameter out of tolerance and entrance spalling is studied. The results show that, with higher feed rate, titanium chips with high temperature and high hardness cause catastrophic erosion of the CFRP-layer, resulting in hole diameter out of tolerance, and increase of entrance spalling. The entrance spalling occurs when the cutting direction and the fibers create a 45 ° angle. Low cutting speed is not suitable for CFRP-layer machining, which worsens the entrance spalling. Therefore, low feed rate and high cutting speed are recommended for drilling of titanium and CFRP layers respectively. Under the premise of enough strength, the drill with larger chip flute is recommended.