The invention discloses an atomic force microscope based five-axis machining device and a method for machining a micro-nano structure on a micro thin-wall spherical surface. The device comprises an AFM (atomic force microscope), a two-dimensional micro-aligning mechanism, a precise air floatation shaft system, a two-dimensional high-precision locating platform and an electric rotating table for driving the AFM to rotate, wherein the two-dimensional micro-aligning mechanism is connected with the upper end of the precise air floatation shaft system, the lower end of the precise air floatation shaft system is connected with the two-dimensional high-precision locating platform, a two-dimensional high-precision locating platform base is fixedly connected on a sample table of the AFM, and the electric rotating table is connected with the AFM. The device and the method adopt the machining advantage of the AFM to solve the problem that the machining range on the surface of the micro thin-wall microsphere is limited and achieve the micro-nano structure machined on the micro thin-wall spherical surface on the basis of the AFM; the machining method is simple without complex machining systems and is simple to operate, and the micro-nano structure with the precision reaching the nanometer magnitude on the surface of the micro thin-wall microsphere can be obtained.