Abstract: Objective To understand the epidemiological characteristics of clustering of hand foot and mouth disease (HFMD) cases in Hongkou and provide evidence for the prevention and control of the disease. Methods The incidence data of clustering of HFMD cases in Hongkou in 2010 were collected to conduct descriptive epidemiological analysis. Results Forty clusterings of HFMD cases were reported, of which 67.5% were reported in child care settings. Up to 97.5% of the clusterings occurred in child care settings. Cox A16 and EV71 were the major pathogens. Conclusion The clustering of HFMD cases could be effectively controlled by strengthening training prevention and conducting early intervention to clustering of HFMD cases in child care settings.