[Objective] This study aimed to improve the water solubility of propolis, and expand the application of propolis in food industry. [Methods] By utilizing the film dispersion method, propolis liposome was prepared with cholesterol and soy lecithin as the wall material and propolis as the core component. The optimal preparation process for propolis liposome was optimized through a combination of one-factor experiments and response surface methodology with the encapsulation rate as the test index, and its antioxidant activity was also analyzed and evaluated. [Results] The optimal process for preparing propolis liposome consisted of 2.5 g/100 mL soy lecithin, a cholesterol to soy lecithin ratio of 1∶10.3, and a cholesterol to propolis ratio of 1∶3.8. These optimized conditions resulted in a high encapsulation rate of 93.09% for propolis liposome. In addition, it was found that the scavenging efficiencies of the 50 μL/mL propolis liposome were 88.60%, 60.53%, and 82.25% for clearance of DPPH radicals, ABTS⁺ radicals, and hydroxyl radicals, respectively. [Conclusion] The prepared propolis liposome has high encapsulation efficiency, good water solubility and good antioxidant capacity.