Compound fruit wine of red pitaya and passion fruit was prepared with red pitaya and passion fruit as the main materials. Using alcohol and sensory scores as evaluation indexes, the fermentation process was optimized with single factor tests and response surface method, the physicochemical indexes, and color parameter, betaerythrin content and 1,1-diphenyl-2-trinitrophenylhydrazine (DPPH) radical scavenging rate during fermentation process were measured. The results showed that the optimal fermentation conditions were as follows: fermentation temperature 22 ℃, initial sugar content 22% and mass ratio of pitaya fruit and passion fruit 100∶10. The physicochemical indexes of compound wine of red pitaya and passion fruit were as follows: total acid 3.73 g/L, pH 3.8, total sugar 54.94 g/L, alcohol content 11.87%vol, methanol 102.17 mg/L, and betaerythrin 105.98 mg/L. The DPPH radical scavenging rate was 61.03%, and the sensory score was 84.72. In the fermentation process, the betaerythrin content, a* value, b* value and DPPH radical scavenging rate all showed a decreasing trend, while the change trend of L* value was not obvious.