Abstract: With fresh honey peach juice and red pitaya juice as the main raw materials, fresh passion fruit juice as the flavoring, the formula of natural compound juice was optimized by single factor test and Box-Behnken response surface methodology based on sensory evaluation. The total viable counts(TVC), total soluble solid(TSS), titrable acid(TA), pH, color, anthocyanin, and V_C content were determined to evaluate the effects of high hydrostatic pressure(HHP, 500 MPa, 10 min) on the quality of natural compound juice in comparison with thermal treated sample(90℃/60 s). The results showed that the optimal formula of natural compound juice was 43% honey peach juice, 46% red pitaya juice, and 11% passion fruit juice. Under the optimization condition, the model predicted that the sensory score was 93.87, and the verification result was 92.86, which was close to that of the model. HHP treatment could effectively inactive microorganisms. Under the treatment of 500 MPa, 10 min, TVC was decreased to 1.84 lg CFU/mL, which was matched up to the national standards of China. HHP had no significant effect on TSS, TA, pH and anthocyanin content(P>0.05). And the anthocyanin content of HHP group was significantly higher than that of thermal treated samples(P<0.05). The browning index of HHP samples was 176.62, which was markedly lower that of thermal treated ones(P<0.05). The content of V_C was decreased by 40.25% with HHP treatment. Compared with thermal treatment, HHP could better maintain the quality and nutritional compounds of natural compound juice.