The high performance liquid chromatography (HPLC) method for the simultaneous determination of 10 polyphenols in papaya wine was optimized and the content of each phenolic substance was analyzed. The results showed that under the optimized chromatographic conditions, 10 polyphenols could be effectively separated within 60 min. All correlation coefficients were more than 0.9936 in the range of 0.1~10 mg/L. The detection limits were between 0.01 and 0.02 mg/L, and the recoveries were between 97.04% and 107.32%.This method was suitable for the simultaneous determination of 10 polyphenols in papaya wine for its high accuracy and reliability. The total polyphenol contents of three kinds of papaya wine were significantly increased (p<0.05) after fermentation for 4 months. The total polyphenol contents of three kinds of papaya wine were 903、1178、1057 mg/100 mL ,respectively. The trend of phenolic compounds in the three kinds of papaya was basically the same as that of the total phenols in the fermentation process. The main polyphenols among the three kinds of papaya wine were catechins, protocatechuic acid and chlorogenic acid. And the content of catechins was the highest (p<0.05), which could be used to distinguish these three papaya.