The color of cyan, magenta, yellow, black, orange and green are used as printing primary colors. The six-color separation model is established based on color subarea theory. Based on the spectral measurement data in an existing six-color printing International Color Consortium (ICC) profile, the Neugebauer equation system in each subarea is established. The gamut compression algorithm based on the node addresses is introduced into the solving process of the Neugebauer equation system in each subarea based on Newton-Raphson method. It successfully solves the problem that the color separation of sampling points outside the target gamut results in the abnormal value. The corresponding six-color ICC profile based on the new color separation model is generated. Subjective evaluation method is used to design the evaluation experiment. Through the longitudinal and transverse evaluation experiments, it is concluded that the proposed six-color separation algorithm and multi-color separation algorithm of mainstream color management software have similar precision. The performance of the separation algorithm can be improved further by perfecting gray component replacement experiment and the correction of Neugebauer equations.