In this study, the changes of volatile components in the fermentation process of traditional medicine-food homologous Yi fermented liquor and their potential effect on the liquor’s medicinal efficacy were analyzed. GC-MS was used to detect and analyze the chemical composition of fermentation samples at different liquor fermentation stages. The main substances influencing flavor were found through the analysis of the types and relative content of flavor compounds in the fermentation process. A total of 58 volatile compounds and 17 amino acid flavor compounds were detected in this research. Among them, the volatile components were divided into 6 categories, including 35 acids, 13 alcohols, 3 esters, 2 phenols, 2 aldehydes and 3 ketones. During the fermentation process, the acids showed a downward trend, from 338.03‰ in the first month to 238.21‰ in the tenth month, whilst other substances showed a downward trend then an upward trend. Alcohols and acids were the most abundant in the third month, reaching 113.10‰ and 232.86‰, respectively. During the fermentation process, citric acid and malic acid had the highest relative contents, which were the most important acid flavor substances and had the greatest impact on the flavor of Yi fermented liquor. This study clarified the changes of flavor compounds and volatile components in fermented liquor during the fermentation process, and also provides a material basis for the optimization and stabilization of the fermentation process in the later stage.