A device and method for detecting wave aberration of a large numerical aperture objective lens, belonging to the field of optical detection, in order to overcome the difficulty of requiring a large numerical aperture high-precision collimator lens in the wavefront detection of a large numerical aperture objective lens, and at the same time improve light energy utilization and detection accuracy , the multimode fiber is located on the object surface of the illumination microscope objective, the diffuser is placed on the illumination microscope mirror plane, the laser light source passes through the multimode optical fiber, the illumination microscope objective and the diffuser in turn to generate ideal spherical waves; The object image plane of the numerical aperture objective lens is placed upside down, placed along the optical axis at the working distance from the image side of the diffuser, the collimator is placed along the optical axis, and its front focal plane coincides with the working object plane of the large numerical aperture objective lens; the microlens The position of the array is conjugate to the exit pupil of the large numerical aperture objective lens relative to the collimator, and the light intensity sensor is placed at the focal plane of the microlens array; when calibrating the systematic error, the spatial filter is placed at the front focal plane of the collimator.