Nickel-based superalloy is a kind of metal material that is widely used to manufacture high-temperature parts in the fields of aviation and aerospace, but it is also a typical difficult-to-machining material. The precision cutting of nickel-based superalloy has always been an important manufacturing problem. Based on the tests of conventional drilling with three kinds of twist drills, the machinability of Inconel 718 was evaluated comprehensively by drilling force, tool wear and machining quality, and the cutting tools suitable for drilling nickel-based superalloy were chosen. Then the experiments of peck-drilling for Inconel 718 were carried out, and the process effect under different peck depth Q was deeply researched. The results showed that the HSS-Co (high speed steel with cobalt) twist drill can meet the needs of low-speed drilling of nickel-based superalloy, while the coated carbide twist drill has better service performance. The drill tip structure of dual clearance angle is beneficial to decrease the cutting friction and improve the machining accuracy. Compared with conventional drilling, the peck-drilling can reduce the cutting force and improve the dimensional accuracy and surface quality. However, it is very important to choose a suitable peck depth Q for fully exploiting the advantages of peck-drilling.