It is not an optimal solution to optimize kerf width of laser cutting Ni-based alloy steel by orthogonal method, so it is suggested to take effects of interaction, which is a combination of factors, into consideration. Design of orthogonal test include evaluation index determination of cutting quality, levels determination of each factor, interaction table top design. After that, in order to avoid test contingency, two groups of orthogonal experiments are performed. L8(2 7) table is used to analyze the effects of gas pressure, defocusing distance, cutting speed and the interaction between the factors on cutting quality, and L16(2 15) table is used to analyze the effects of cutting speed, current, pulse width, frequency and the interaction between the factors on cutting quality. Finally, according to the test results, We can get a conclusion that interaction analysis can accurately find the optimal solution in a comprehensive experiment by a contrast of intuitive analysis and interaction analysis. The significant interaction that impacts on quality of laser cutting Ni-based alloy steel is summarized. The optimum technological parameters of the two groups and important factors are obtained.