Objective To study the features of hand, foot and mouth disease (HFMD) with liver damage and investigate the possible related factors and improve the understanding of liver damage in HFMD patients. Methods The clinical data of 57 HFMD patients admitted from 2015 to 2018 were collected to retrospectively analyze the clinical features of liver damage, as well as routine blood test, C-reactive protein (CRP), liver function. Categorical data were analyzed by chi-square test. Continuous data were expressed as mean±standard deviation; comparison between groups was made by t test and multivariate stepwise regression analysis. Results The incidence of abnormal alanine aminotransferase (ALT) level in 57 cases was 33.3%, and 68.4% of these patients had a serum ALT level of less than 200 IU /L. Platelet count were not found to be related to liver damage ( t=1.65, P=0.105 ). There was significant difference in white blood cell (WBC) count and CRP between patients with liver damage and controls ( t=3.86, P=0.001; t=2.36, P=0.022). Simultaneous increase in WBC count was significantly associated with an increased risk of liver damage (P＜0.05). Conclusion CRP and platelet count are not found to be significantly related to the development of liver damage, but there is a close relationship between liver damage and WBC count. WBC count shows a certain relationship with liver damage. Clinicians should pay attention to these factors and take timely measures for intervention.