Abstract: Single crystal Ni-based alloys possess excellent properties such as high temperature resistance, high strength and high toughness. Thses mechanical properties are affected by secondary orientation and cooling holes induced during complex manufacturing processes. The current research mainly focuses on the deformation mechanism and mechanical response of plates with one hole. While, the plate with multiple holes is often used in engineering. At present, it is urgent to clarify the deformation mechanism of the plate with multiple holes, the secondary orientation effect, and the strain gradient effect caused by cooling holes. In this paper, a nonlocal crystal plasticity constitutive model based on the dislocation mechanism is used to numerically simulate the uniaxial tensile deformation behavior of the Ni-based single crystal plate with cooling holes. A dislocation flux term is derived based on the relationship between the plastic slip gradient and geometrically necessary dislocations, enabling this crystal plasticity model to effectively describe the strain gradient effect. In order to comprehensively reveal the secondary orientation effect of Ni-based alloys with cooling holes, this paper systematically studies the uniaxial tensile deformation behavior of sheets with 100 and 110 orientations (two secondary orientations). The influence of the number of holes on the plastic behavior of the plate with two secondary orientations is investigated. By analyzing the variation of the resolved stress on slip systems, activation of the dominant slip systems and the evolution of geometrically necessary dislocation density during the deformation of Ni-based alloy plates, the effects of plastic slip and its distribution on the strength of Ni-based alloy plates with different secondary orientations are discussed. The results show that the tensile strength of 110 plate is lower than that of 100 plate. Furthermore, the plastic deformation process of the five-hole plate is more complicated than that of the one-hole plate and is easier to be affected by secondary orientation. Finally, the location of the slip gradient is mainly located near the cooling hole and the plastic slip zone. The research results can provide theory basis for the design and service of Ni-based alloys in engineering.