The invention belongs to the technical field of defoamers and discloses a polyether modified organic silicon defoamer safe to strains and a preparation method thereof. The preparation method includesthe following steps that: silicon dioxide nanometer microspheres, dimethyl silicone oil, DMF and deionized water are sequentially added into a reaction flask, ammonia water is added while stirring isconducted, heating is conducted to 50-70 DEG C, a reaction is conducted for 1-2 hours, cooling is conducted to the room temperature, and centrifugation is conducted, a precipitate is washed with ethanol, and drying is performed to obtain dimethicone grafted and modified silicon dioxide nano microspheres; 30-60 parts of the dimethicone grafted and modified silicon dioxide nano microspheres, 30-50 parts of polyether modified silicon oil, 1-10 parts of a thickener, 2-10 parts of an emulsifier and 10-50 parts of water are added into a dispersion tank, heating is conducted to 180-200 DEG C, stirring is performed for 2-3 hours, gradient cooling is carried out to 50-60 DEG C in a stirring state, and finally natural cooling is performed to obtain the polyether modified organic silicon defoamer. The defoamer has the advantages of being low in surface tension, high in defoaming speed, long in foam inhibition time, small in dosage, free of toxicity and harm to strains, wide in application range and the like.