A method of ion beam processing based on optical microscopy imaging, comprising: marking (S100) a surface of a sample using an ion beam, so as obtain a registration reference pattern; performing (S110) a three-dimensional optical imaging on the sample to obtain a first three-dimensional light microscopy image; projecting (S120) the first three-dimensional light microscopy image to a cutting angle of the ion beam, and determining a first position of a to-be-researched target in the first three-dimensional light microscopy image based on the registration reference pattern; and performing (S130) an ion beam imaging on the sample to obtain an image excited by an ion beam, and determining, according to the first position, a second position of the to-be-researched target in the image excited by the ion beam, wherein the method further comprises: thinning (S240) the sample according to the second position to obtain a second slice containing the to-be-researched target; characterised in that the method further comprises: performing (S250) a three-dimensional optical imaging on the second slice to obtain a second three-dimensional light microscopy image, wherein a magnification of the three-dimensional optical imaging on the second slice is greater than a magnification of the three-dimensional optical imaging on the sample; projecting (S260) the second three-dimensional light microscopy image to the cutting angle of the ion beam to obtain a two-dimensional projection image; determining a third position of the to-be-researched target in the second slice based on the two-dimensional projection image; and thinning (S270) the sample according to the third position to obtain a third slice containing the to-be-researched target. marking (S100) a surface of a sample using an ion beam, so as obtain a registration reference pattern; performing (S110) a three-dimensional optical imaging on the sample to obtain a first three-dimensional light microscopy image; projecting (S120) the first three-dimensional light microscopy image to a cutting angle of the ion beam, and determining a first position of a to-be-researched target in the first three-dimensional light microscopy image based on the registration reference pattern; and performing (S130) an ion beam imaging on the sample to obtain an image excited by an ion beam, and determining, according to the first position, a second position of the to-be-researched target in the image excited by the ion beam, wherein the method further comprises: thinning (S240) the sample according to the second position to obtain a second slice containing the to-be-researched target; characterised in that the method further comprises: performing (S250) a three-dimensional optical imaging on the second slice to obtain a second three-dimensional light microscopy image, wherein a magnification of the three-dimensional optical imaging on the second slice is greater than a magnification of the three-dimensional optical imaging on the sample; projecting (S260) the second three-dimensional light microscopy image to the cutting angle of the ion beam to obtain a two-dimensional projection image; determining a third position of the to-be-researched target in the second slice based on the two-dimensional projection image; and thinning (S270) the sample according to the third position to obtain a third slice containing the to-be-researched target. <EOS>