The invention relates to a hyaluronic acid mixed gel containing amphiphilic microspheres for injection and a preparation method thereof. The microsphere material involves amphiphilic materials such as PLLA-PEG, PLGA, and PLGA-PEG. The molecular weight of PLLA or PLGA is 10,000-500,000, and that of PEG is 1,000-10,000. In PLGA, LA / GA=90 / 10-10 / 90. The average particle size of the microspheres is 1-200 μm, and the mass fraction in the gel is 1-50%; the gel component is hyaluronic acid, or hyaluronic acid cross-linked with divinyl sulfone or glycidyl ether, The molecular weight of hyaluronic acid is 100,000-3,000,000, and the mass fraction is 1-50%. The gel component can also be animal-derived collagen, chitosan, amino acid cellulose, sodium alginate, and the like. The microsphere mixed gel is prepared in a sodium chloride solution or a phosphate buffer solution with an osmotic pressure of 250-350 mOsm / L and a pH of 6.5-7.5. In the present invention, the amphiphilic microspheres are directly mixed with the hyaluronic acid gel, and the amphiphilic microspheres are easily and uniformly distributed in the gel, and after being injected into the human body, they are not easy to assemble into lumps in the water environment of the human body.