Polyether-ether-ketone (PEEK) has been widely applied in various fields due to its excellent mechanical properties and biocompatibility. The efficient and high-quality customized manufacturing of PEEK components are investigated in this study by the hybrid 3D printing and milling process. At first, the alternating hybrid process is selected and verified by comparing two typical hybrid process categories and conducting experiments, respectively. Second, a set of procedures are designed to automate the engineering application of the hybrid process trying to avoid the disadvantages of manual programing. Then, considering the tool length and possible interferences during the hybrid process, a model segmentation algorithm, namely, the exchange principle of avoiding interference (EPAI) is proposed. Based on the introduced EPAI and the programing language Python, the additive and subtractive hybrid manufacturing (ASHM) data processing procedure is proposed and realized by post-processing of the conventional 3D printing codes. Finally, the feasibility experiments have been conducted. The experimental results verify the hybrid manufacturing process in the fabrication of parts with complex internal features. The surface roughness Ra and dimensional error L of the parts have been reduced by 75.5% and 85.2%, respectively, while the shear strength τ has been increased by 14.1%. Compared with conventional milling process, the material consumption is reduced by 48.7%.