Abstract: Objective To determine the intestinal flora structure and change characteristics of infants with hand-foot-mouth disease(HFMD).Methods A total of 48 infants who were diagnosed with HFMD in Suqian Hospital Affiliated to Xuzhou Medical University from January 2021 to June 2022 were set as a HFMD group, while 20 healthy infants were selected as a control group. Their fecal DNA was extracted for 16S rDNA amplification sequencing. The abundance, diversity and structure of this biological information were analyzed.Results According to α and β diversity analysis, there was no difference in the abundance and diversity of intestinal flora between the two groups. LEfSe analysis showed that the intestinal flora structure in the HFMD group changed, where abundance of Lachnospira and Veillonella decreased, while the abundance of Megamonas and Escherichia increased.Conclusions HFMD infants show changes in intestinal flora, and the bacteria producing acetate and propionate in the intestinal tract are reduced. These finding may provide theoretical basis for exploring the pathogenesis and investigating the microecological intervention of HFMD.