A high-precision alignment method of off-axis Cassegrain optical system was provided. According to the assembly difficulties of off-axis paraboloid primary mirror, the bonding form and area are determined by theoretical calculation and simulation analysis. The self-alignment detection is performed by ainterferometer and a plane mirror to complete the micro-stress of assembly of primary mirror. Combined with the structural characteristics of the system, the relationship between the primary mirror position attitude and the mechanical reference is established by measuring the optimal surface shape of the primary mirror, so that the primary mirror optical axis is consistent with the mechanical reference. By analyzing the relationship between the amount of secondary mirror misalignment and the system wavefront aberration, the system wavefront aberration correction is realized by adjusting the secondary mirror by six degrees of freedom. The surface shape change after the primary mirror is bonded and assembled is less than 5%, and the wave aberration after the system aligned is better than 0.055λ. The data meets the design index requirements.