Abstract: Objective　We aimed to compare the clinical and etiological features of hand, foot, and mouth disease (HFMD) with or without facial rash. Methods　Clinical data of children with HFMD reported from January to December 2016 and pathogen test results of some children were retrospectively analyzed. The children were divided into two groups based on whether it is combined with facial rashes or not. Results　A total of 1134 cases of atypical HFMD with facial rash were enrolled, accounting for 9.92% of all HFMD cases (1134/11430), which easily occurring among children under one year of age and over 3 years old. The clinical symptoms of cases with facial rash were milder than those without facial rash, and the incidence of fever and nervous system complications were lower. Coxsackievirus A6 infection was predominant, and the ratio was significantly higher than that without facial rash (P<0.05). Conclusions　The majority of HFMD with facial rashes was caused by Coxsackie virus A6 infection and its clinical symptoms were mild and atypical.