The invention discloses a compound feed for preventing fatty liver of tilapia and a preparation method of the feed. The compound feed is prepared from the following raw materials according to a certain proportion: fish meal, fermented soybean meal, meat and bone meal, rapeseed meal, cottonseed meal, wheat bran, wheat flour, calcium dihydrogen phosphate, multi-vitamin premix, multi-mineral premix, soybean oil, soybean lecithin, chitosan oligosaccharide, astragalus polysaccharide and choline chloride. The preparation comprises the following steps of: respectively crushing and screening all the raw materials (except the soybean oil) by a crushing machine, weighing the flour, the calcium dihydrogen phosphate, the multi-vitamin premix, the multi-mineral premix, the soybean lecithin, the chitosan oligosaccharide, the astragalus polysaccharide, the choline chloride and other raw materials according to the mass fraction in the formula and mixing uniformly, further weighing the remaining raw materials, uniformly stirring and mixing, fully uniformly mixing with water, performing extrusion and pelletization by a feed machine, and drying at the temperature of 55-60 DEG C to prepare the feed for the tilapia. The compound feed has balanced nutrition, is suitable for requirements of healthy growth of the tilapia and can further reduce the accumulation of fat in livers of the tilapia and improve disease resistance of the tilapia.