The invention discloses a method for producing a microsphere through an oil-in-nanoparticle suspension and water-in-oil mode. The method comprises the following steps that medicine aqueous solution is added into polymer organic solution to be emulsified, nanoparticle suspension is then selected as a surfactant sphere, the mixture is hardened in another water phase finally, the organic solution is removed and the microsphere is collected. The produced microsphere contains the medicine, the nanoparticle, the polymer and pharmaceutic adjuvant, the contents of the medicine, the nanoparticle, the polymer and the pharmaceutic adjuvant are respectively as follows in weight percent: 0.01-40% of the medicine, 0.01-96% of the nanoparticle, 99.98-3.65% of the polymer and 0-30% of the pharmaceutic adjuvant. The method avoids the tissue compatibility problem caused by the microsphere which is produced through a conventional water (W)/oil (O), W/O/W and S (sphere)/O/O method; and moreover, the microsphere which has a nanoparticle assembled surface and is produced through the method has a function of increasing cell adhesion, inflammation and microencapsulation which are caused by local peracid and hydrophobic materials can be reduced, and the method can be applied to the preparation of various drug sustained-release or controlled-release microspheres and disease treatment.