Abstract: The disclosure provides a method to improve the solubility of double hydrophobic proteins in water. The method includes: 1) adding a first hydrophobic protein and a second hydrophobic protein to distilled water, stirring, adding an aqueous alkali to the mixture until the pH of the mixture is greater than or equal to 10.0; 2) stirring the mixture for 30-120 min at 500-2000 rpm; 3) stirring the mixture obtained from 2) for 45-75 min at 500-2000 rpm and meanwhile dropwise adding an acid solution to the mixture until the pH of the mixture is 7.0, to yield a first solution; 4) dialyzing the first solution of the acid solution and the mixture in 3) for 20-30 hours, to yield a second solution; 5) centrifuging the second solution obtained from 4) at 4000-10000×g for 10-30 min, and collecting a supernatant; and 6) freezing and drying the supernatant.