Conventional laser processing of metals will form serious heat affected zone, micro cracks, burrs and recast layer, resulting in rough machined surface and serious slag accumulation. As a new type of laser-waterjet composite processing method, waterjet guided laser can reduce or even eliminate heat affected zone, thermal crack, recast layer and burr. It has the advantages of high surface quality, strong depth ability and large depth-to-diameter ratio structure. Nickel-based single crystal superalloy is widely used in advanced aero-engine turbine blades for their excellent overall performance. With waterjet guided laser processing technology, this paper study the influence of process parameters on the grooving morphology and quality of DD6 nickel-based single crystal superalloy. A multi-factor study on the influence of laser power, laser repetition frequency, waterjet velocity and feeding speed on grooving was carried out with a self-developed waterjet guided laser processing device. The depth-to-width ratio and sidewall taper of the machined groove were measured and analyzed by using a three-dimensional confocal laser scanning microscope. The experimental results show that the grooves taper can be decreased with reducing the laser repetition frequency and increasing the laser power. The grooves large depth processing is improved by reducing the feeding speed, increasing the laser power, reducing the laser repetition frequency and increasing the waterjet velocity. The cutting experiment of 1 mm DD6 nickel-based single crystal superalloy was achieved with better processing process parameters, and it was found that the upper and lower surface roughness of the cutting surface was inconsistent, providing a theoretical basis for the study of high quality processing of nickel-based single-crystal superalloy by waterjet guided laser.