Abstract: Objective To analyze the epidemiological characteristics and temporal-spatial clustering of hand, foot and mouth disease (HFMD) in Guangxi from 2008 to 2015, and to provide evidence for the prevention and control of the disease. Methods Surveillance information of HFMD at the county level was collected from Chinese National Notifiable Infectious Disease Report System. The epidemiological characteristics were described using Excel 2010. SaTScan 9.4.2 was used to detect the potential temporal-spatial clusters. By setting different population percentages as the maximum spatial cluster sizes in the analysis, multiple models were assessed to select the optimal one. Results From 2008 to 2015, all cities in Guangxi had reported HFMD cases, a total of 1 360 857 cases were reported with an annual incidence of 359.61 per 10 000. The main peak incidence was observed from April to July, followed by a second peak from September to November. Incidence rate of male was higher than female, children aged 0-5 years accounted for 92.28% of the total cases. The effect of setting the population percentage as the maximum spatial cluster size varied in different models, among which 10% of the population at risk was the best mode. The counties of Nanning and Liuzhou were the main grade-I gathering areas and grade-Ⅱ gathering areas, respectively. The gathering time were mainly detected from March to July. Conclusions Incidence of HFMD was still high in Guangxi. HFMD had obvious aggregation in space and time. We should strengthen prevention and control of HFMD in Nanning and Liuzhou during gathering time.