Abstract： Objective The purpose of this study was to explore the spatial clustering,specific clustering areas,as well as changing trend of clustering areas of hand-foot-mouth disease (HFMD).Methods Exploratory spatial data analysis (ESDA) was used to conduct spatial statistical analyses for the HFMD using 2008-2011 data at both provincial and county/district levels.Results The Global Moran' s I coefficients appeared to be 0.3336,0.6074,0.3372,0.4620 and 0.4367 for 2008-2011and for the combined 4 years,respectively.The corresponding P-values were 0.002,0.001,0.004,0.001 and 0.001 respectively,when using the Monte Carlo tests with all the P-values less than 0.05.Moran' s Ⅰ coefficients ranged between 0.3 and 0.7,showing the appearance of moderate or higher clustering nature.Based on the results from nationwide analyses on clustering areas at the county/district levels between 2008 and 2011 (Moran' s I=0.5198,P=0.001),it appeared a moderate clustering nature.When local autocorrelation analysis was applied at the provincial level,3 hot spot areas in Beijing,Tianjin and Shanghai cities in 2008；7 hot spot areas in Beijing,Tianjin,Hebei,Shanxi,Shanghai,Jiangsu and Shandong in 2009; four hot spot areas:Beijing,Tianjin,Guangdong and Guangxi; five hot spot areas:Fujian,Jiangxi,Hunan,Guangdong and Guangxi in 2011,were discovered.390 hot-spot counties/districts were found through local autocorrelation analyses using the three-year data of 2008 to 2010.Conclusion Spatial clustering nature of HFMD incidence between 2008 and 2011 in China appeared to be moderate or high,with the clustered areas a north to south shifting trend.However,further investigation was in need to address this changing trend.