The invention discloses a high-efficiency environment-friendly compound feed for culturing litopenaeus vannamei at low salinity and a preparation method of the high-efficiency environment-friendly compound feed. The high-efficiency environment-friendly compound feed comprises fish meal, fly maggot powder, chicken meal, mycoprotein powder, acidolysis feature meal, nucleic acid yeast, soybean meal, peanut bran, meat and bone meal, shrimp shell meal, cottonseed meal, squid organ meal, high protein flour, soya bean lecithin, sea fish oil, choline chloride, vitamin C-phosphate, monocalcium phosphate, magnesium sulfate heptahydrate, potassium chloride, potassium citrate, compound multi-vitamin, compound mineral salt, and other components according to a special proportion. Cultivation tests prove that the high-efficiency environment-friendly compound feed provided by the invention is capable of completely meeting the nutrition demand of healthy growth of litopenaeus vannamei under the condition of low salinity, and has multiple advantages of effectively promoting the healthy, quick and effective growth of the litopenaeus vannamei, reducing emissions of nitrogen, phosphorus and the like to be beneficial to the environmental protection, being stable in raw material sources, low in cost, simple in preparation process and strong in maneuverability, effectively ensuring the water body stability and the bioavailability of produced litopenaeus vannamei, and the like.